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  • 301. Feldthusen, Caroline
    et al.
    Grimby-Ekman, Anna
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Jacobsson, Lennart
    Mannerkorpi, Kaisa
    Seasonal variations in fatigue in persons with rheumatoid arthritis: a longitudinal study2016Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, artikel-id 59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Fatigue is a prominent symptom in persons with rheumatoid arthritis (RA). Although this symptom has been described to vary in duration and frequency little is known about fluctuations in fatigue over time and season. The aim of this study was to describe monthly and seasonal variations in fatigue, in persons with RA of working age.

    Methods: Sixty-five participants diagnosed with RA and aged 20-65 years were recruited from a rheumatology clinic in Sweden. The participants provided self-assessments of their fatigue at seven time points during the four seasons using a 0-100 mm visual analogue scale (VAS) and the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ). Multiple regression analysis using mixed models was used to analyze changes in fatigue over time.

    Results: The mean +/- SD of fatigue rated on the VAS was 51 +/- 13, indicating substantial fatigue. Analysis of monthly variation showed statistically significant variation in fatigue ratings concerning VAS fatigue score (p < 0.01) as well as the BRAF-MDQ total score and Living, Cognition (p < 0.001), and Physical (p < 0.05) sub-scores, but not the BRAF-MDQ Emotional sub-score. The greatest variations were seen from January to September, with higher fatigue ratings in January. The changes in VAS fatigue scores over time were considered to be of clinical importance. Analysis of seasonal variation revealed a statistically significant seasonal variation in fatigue levels, with higher fatigue values during the winter as measured by VAS fatigue score (p < 0.01) as well as BRAF-MDQ total score (p < 0.01) and Physical and Living sub-scores (both p < 0.01). The greatest variation was seen between winter and autumn for VAS fatigue and between winter and summer for BRAF-MDQ total score and Physical and Living sub-scores. There were no statistical differences in fatigue levels, monthly or seasonal, between sexes or age groups.

    Conclusions: The majority of rating scales used in this study showed fluctuations in fatigue, general and physical fatigue being significantly greater during the winter. As fatigue is a substantial symptom in many persons with RA, this information is important for rheumatology professionals when dealing with persons with RA in routine care.

  • 302. Fernandes-Cerqueira, Catia
    et al.
    Ossipova, Elena
    Gunasekera, Sunithi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Hansson, Monika
    Mathsson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Catrina, Anca I.
    Sommarin, Yngve
    Klareskog, Lars
    Lundberg, Karin
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Jakobsson, Per-Johan
    Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens2015Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 17, artikel-id 155Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: We have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides, and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA). Methods: The autoantigenic potential of the fibrinogen peptides was investigated by screening 927 serum samples from the Epidemiological Investigation of RA (EIRA) cohort on a peptide microarray based on the ImmunoCAP ISAC (R) system. In order to assay for ACPA blocking, two independent pools of purified ACPA were incubated with the respective targeting peptide prior to binding to cyclic citrullinated peptide (CCP) 2 using the CCPlus (R) ELISA kit. Results: Two peptides derived from the fibrinogen a chain, Arg573Cit (563-583) and Arg591Cit (580-600), referred to as Cit573 and Cit591, and two peptides from the fibrinogen beta chain, Arg72Cit (62-81) and Arg74Cit (62-81) (Cit72 and Cit74), displayed 65 %, 15 %, 35 %, and 53 % of immune reactivity among CCP2-positive RA sera, respectively. In CCP2-negative RA sera, a positive reactivity was detected in 5 % (Cit573), 6 % (Cit591), 8 % (Cit72), and 4 % (Cit74). In the competition assay, Cit573 and Cit591 peptides reduced ACPA binding to CCP2 by a maximum of 84 % and 63 % respectively. An additive effect was observed when these peptides were combined. In contrast, Cit74 and Cit72 were less effective. Cyclization of the peptide structure containing Cit573 significantly increased the blocking efficiency. Conclusions: Here we demonstrate extensive autoantibody reactivity against in vivo citrullinated fibrinogen epitopes, and further show the potential use of these peptides for antagonizing ACPA.

  • 303.
    Ferrannini, Giulia
    et al.
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden.;Univ Turin, Postgrad Sch Internal Med, Dept Med Sci, Turin, Italy..
    Svenungsson, Elisabet
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden..
    Kjellstrom, Barbro
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Elvin, Kerstin
    Karolinska Inst, Dept Clin Immunol & Transfus Med, Unit Clin Immunol, Stockholm, Sweden..
    Grosso, Giorgia
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden..
    Näsman, Per
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Fastigheter och byggande, Bygg- och fastighetsekonomi.
    Ryden, Lars
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Norhammar, Anna
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden.;Capio St Gorans Hosp, Stockholm, Sweden..
    Dysglycaemic patients with antiphospholipid antibodies IgG: a neglected group at high cardiovascular risk?2019Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 28, s. 42-42Artikel i tidskrift (Övrigt vetenskapligt)
  • 304. Fisher, Benjamin A.
    et al.
    Plant, Darren
    Brode, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    van Vollenhoven, Ronald F.
    Mathsson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Symmons, Deborah
    Lundberg, Karin
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Venables, Patrick J.
    Antibodies to citrullinated α-enolase peptide 1 and clinical and radiological outcomes in rheumatoid arthritis2011Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 70, nr 6, s. 1095-1098Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION:

    The anticyclic citrullinated peptide 2 (anti-CCP2) assay is a generic test for antibodies to citrullinated proteins, among which there is a subset of about 50% with antibodies to citrullinated enolase peptide 1 (CEP-1). The anti-CEP-1 positive subset is strongly associated with the HLA-DRB1 shared epitope and its interaction with smoking.

    OBJECTIVE:

    To investigate whether anti-CEP-1 antibodies may be helpful in predicting outcome.

    METHODS:

     Anti-CEP-1 and anti-CCP2 antibodies were measured in two prospective cohorts of patients (Karolinska n=272, Norfolk Arthritis Register (NOAR) n=408) with early rheumatoid arthritis (RA). Outcomes measured were C-reactive protein, erythrocyte sedimentation rate, visual analogue scales for pain and global assessment of disease activity, Health Assessment Questionnaire, physician's assessment, swollen and tender joint counts and radiological progression.

    RESULTS:

     Anti-CCP2 antibodies were present in 57% and 50%, and anti-CEP-1 in 27% and 24% of the Karolinska and NOAR cohorts, respectively. Importantly, no statistically significant differences in clinical outcomes were demonstrated between the anti-CEP-1-/CCP2+ and the anti-CEP-1+/CCP2+ subsets in either cohort, or in radiological outcomes in the Karolinska cohort.

    CONCLUSION:

     Although antibodies to specific citrullinated proteins may have distinct genetic and environmental risk factors, the similarity in clinical phenotype suggests that they share common pathways in the pathogenesis of joint disease in RA.

     

  • 305.
    Foeldvari, Ivan
    et al.
    Hamburg Ctr Pediat & Adolescent Rheumatol, Hamburg, Germany.
    Klotsche, Jens
    German Rheumatism Res Ctr, Program Area Epidemiol, Berlin, Germany.
    Kasapcopur, Ozgur
    Istanbul Univ, Cerrahpasa Med Sch, Dept Pediat Rheumatol, Istanbul, Turkey.
    Adrovic, Amra
    Istanbul Univ, Cerrahpasa Med Sch, Dept Pediat Rheumatol, Istanbul, Turkey.
    Torok, Kathryn S.
    UPMC, Childrens Hosp Pittsburgh, Scleroderma Ctr Pittsburgh, Pediat Rheumatol, Pittsburgh, PA USA.
    Stanevicha, Valda
    Riga Stradins Univ, Pediat Cathedra, Riga, Latvia.
    Sztajnbok, Flavio
    Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
    Terreri, Maria Teresa
    UNIFESP Univ Fed Sao Paulo, Fed Univ Sao Paulo, Pediat Rheumatol Unit, Sao Paulo, Brazil.
    Alexeeva, Ekaterina
    Natl Med Res Ctr Childrens Hlth, Moscow, Russia;Sechenov First Moscow State Med Univ, Minist Hlth Russian Federat, Moscow, Russia.
    Anton, Jordi
    Hosp St Joan de Deu, Barcelona, Spain.
    Katsicas, Maria M.
    Hosp Pediat Prof Dr JP Garrahan, Serv Immunol & Rheumatol, Buenos Aires, DF, Argentina.
    Smith, Vanessa
    Univ Ghent, Dept Internal Med, Ghent Univ Hosp, Dept Internal Med,Dept Rheumatol, Ghent, Belgium.
    Avcin, Tadey
    Univ Childrens Hosp, Ljubljana, Slovenia.
    Cimaz, Rolando
    Osped Pediat Anna Meyer, Pediat, Florence, Italy.
    Kostik, Mikhail
    St Petersburg State Pediat Med Univ, St Petersburg, Russia.
    Lehman, Thomas J. A.
    Weill Cornell Med Coll, Hosp Special Surg, Pediat Rheumatol, New York, NY USA.
    Sifuentes-Giraldo, Walter A.
    Univ Hosp Ramon y Cajal, Dept Rheumatol, Madrid, Spain.
    Appenzeller, Simone
    State Univ Campinas UNICAMP, Fac Med Sci, Sao Paulo, Brazil.
    Janarthanan, Mahesh
    Nemkova, Dana
    Gen Univ Hosp Prague, Dept Pediat & Adolescent Med, Pediat Rheumatol Unit, Prague, Czech Republic.
    Santos, Maria Jose
    Reuma Pt, Almada, Portugal.
    Battagliotti, Cristina
    Hosp Ninos Dr Orlando Alasia, Santa Fe, Argentina.
    Berntson, Lillemor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Bica, Blanca
    Univ Fed Rio de Janeiro, HUCFF, Serv Reumatol, Rio De Janeiro, Brazil.
    Brunner, Juergen
    Med Univ Innsbruck, Div Pediat Rheumatol, Innsbruck, Austria.
    Reis, Patricia Costa
    Hosp Santa Maria, Pediat, Lisbon, Portugal.
    Eleftheriou, Despina
    UCL Inst Child Hlth, Infect Inflammat & Rheumatol, London, England.
    Harel, Liora
    Tel Aviv Univ, Sackler Sch Med, Schneider Childrens Med Ctr Israel, Tel Aviv, Israel.
    Horneff, Gerd
    Asklepios Kinderklin St Augustin GmbH, St Augustin, Germany.
    Kallinich, Tilmann
    Charite Berlin Campus Virchow, Berlin, Germany.
    Lazarevic, Dragana
    Clin Ctr Nis, Dept Pediat Rheumatol & Immunol, Nish, Serbia.
    Minden, Kirsten
    Childrens Univ Hosp Charite, German Rheumatism Res Ctr Berlin, Berlin, Germany.
    Nielsen, Susan Mary
    Rigshosp, Copenhagen, Denmark.
    Uziel, Yosef
    Meir Med Ctr, Kefar Sava, Israel.
    Helmus, Nicola
    Hamburg Ctr Pediat & Adolescent Rheumatol, Hamburg, Germany.
    Update from the Juvenile Scleroderma Inception Cohort2018Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70Artikel i tidskrift (Övrigt vetenskapligt)
  • 306.
    Foeldvari, Ivan
    et al.
    Hamburg Ctr Pediat & Adolescent Rheumatol, Hamburg, Germany.
    Klotsche, Jens
    German Rheumatism Res Ctr, Program Area Epidemiol, Berlin, Germany.
    Kasapcopur, Ozgur
    Istanbul Univ, Cerrahpasa Med Sch, Dept Pediat Rheumatol, Istanbul, Turkey.
    Terreri, Maria Teresa
    UNIFESP Univ Fed Sao Paulo, Fed Univ Sao Paulo, Pediat Rheumatol Unit, Sao Paulo, Brazil.
    Avcin, Tadey
    Univ Childrens Hosp, Ljubljana, Slovenia.
    Cimaz, Rolando
    Osped Pediat Anna Meyer, Pediat, Florence, Italy.
    Kostik, Mikhail
    St Petersburg State Pediat Med Univ, St Petersburg, Russia.
    Katsicas, Maria M.
    Hosp Pediat Prof Dr JP Garrahan, Serv Immunol & Rheumatol, Buenos Aires, DF, Argentina.
    Nemkova, Dana
    Gen Univ Hosp Prague, Dept Pediat & Adolescent Med, Pediat Rheumatol Unit, Prague, Czech Republic.
    Battagliotti, Cristina
    Hosp Ninos Dr Orlando Alasia, Santa Fe, Argentina.
    Berntson, Lillemor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Brunner, Juergen
    Med Univ Innsbruck, Div Pediat Rheumatol, Innsbruck, Austria.
    Harel, Liora
    Tel Aviv Univ, Sackler Sch Med, Schneider Childrens Med Ctr Israel, Tel Aviv, Israel.
    Kallinich, Tilmann
    Charite Berlin Campus Virchow, Berlin, Germany.
    Minden, Kirsten
    Charite Univ Med Berlin, Berlin, Germany.
    Santos, Maria Jose
    Reuma Pt, Almada, Portugal.
    Torok, Kathryn S.
    Univ Pittsburgh, Med Ctr, Pediat Rheumatol, Pittsburgh, PA USA.
    Helmus, Nicola
    Hamburg Ctr Pediat & Adolescent Rheumatol, Hamburg, Germany.
    After 24 Months Observation Period the Patients Related Outcomes Improve Significantly in the Juvenile Scleroderma Inceptions Cohorte2018Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70Artikel i tidskrift (Övrigt vetenskapligt)
  • 307.
    Folkersen, Lasse
    et al.
    Department of Bioinformatics, Technical University of Denmark, Lyngby, Denmark.; Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Brynedal, Boel
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Diaz-Gallo, Lina Marcela
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Ramsköld, Daniel
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Shchetynsky, Klementy
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Westerlind, Helga
    nstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Sundström, Yvonne
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Schepis, Danika
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Hensvold, Aase
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Vivar, Nancy
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Eloranta, Maija-Leena
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Brunak, Søren
    Department of Bioinformatics, Technical University of Denmark, Lyngby, Denmark.
    Malmström, Vivianne
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Catrina, Anca
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Moerch, Ulrik Gw
    Klareskog, Lars
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Padyukov, Leonid
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Berg, Louise
    Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Integration of known DNA, RNA and protein biomarkers provides prediction of anti-TNF response in rheumatoid arthritis: results from the COMBINE study.2016Ingår i: Molecular medicine (Cambridge, Mass. Print), ISSN 1076-1551, E-ISSN 1528-3658, Vol. 22, s. 322-328Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results have been discrepant with few successful replications. Our objective was to build a biobank with DNA, RNA and protein measurements to test the claim that the current state-of-the-art precision medicine will benefit RA patients.

    METHODS: We collected 451 blood samples from 61 healthy individuals and 185 RA patients initiating treatment, before treatment initiation and at a 3 month follow-up time. All samples were subjected to high-throughput RNA sequencing, DNA genotyping, extensive proteomics and flow cytometry measurements, as well as comprehensive clinical phenotyping. Literature review identified 2 proteins, 52 single-nucleotide polymorphisms (SNPs) and 72 gene-expression biomarkers that had previously been proposed as predictors of TNF inhibitor response (∆DAS28-CRP).

    RESULTS: From these published TNFi biomarkers we found that 2 protein, 2 SNP and 8 mRNA biomarkers could be replicated in the 59 TNF initiating patients. Combining these replicated biomarkers into a single signature we found that we could explain 51% of the variation in ∆DAS28-CRP. This corresponds to a sensitivity of 0.73 and specificity of 0.78 for the prediction of three month ∆DAS28-CRP better than -1.2.

    CONCLUSIONS: The COMBINE biobank is currently the largest collection of multi-omics data from RA patients with high potential for discovery and replication. Taking advantage of this we surveyed the current state-of-the-art of drug-response stratification in RA, and identified a small set of previously published biomarkers available in peripheral blood which predicts clinical response to TNF blockade in this independent cohort.

  • 308.
    Forsblad d'Elia, Helena
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Christgau, Stephan
    Mattsson, Lars-Ake
    Saxne, Tore
    Ohlsson, Claes
    Nordborg, Elisabeth
    Carlsten, Hans
    Hormone replacement therapy, calcium and vitamin D3 versus calcium and vitamin D3 alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456].2004Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 6, nr 5, s. R457-68Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.

  • 309.
    Forsblad d'Elia, Helena
    et al.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Rehnberg, E
    Kvist, G
    Ericsson, A
    Konttinen, Yt
    Mannerkorpi, K
    Fatigue and blood pressure in primary Sjogren's syndrome2008Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 37, nr 4, s. 284-292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Primary Sjogren's syndrome (SS) is an autoimmune disease characterized by fatigue. Little is known about the genesis of fatigue. Fatigue is thought to represent a multidimensional concept and it is important to be able to measure it confidently. The aims were to evaluate the reliability and validity of the 20-item Multidimensional Fatigue Inventory (MFI-20) in SS and to search for factors associated with this disabling symptom.

    METHODS: Forty-eight women with primary SS completed the MFI-20 questionnaire. The results were compared with age-matched women with fibromyalgia (FM) and healthy controls. Convergent construct validity was assessed by correlations to a Visual Analogue Scale (VAS) for global fatigue by Spearman's correlation (r(s)). Test-retest reliability was analysed by the intraclass correlation coefficient (ICC) in 28 women. Associations between clinical variables and subscales of the MFI-20 were analysed.

    RESULTS: The SS women scored significantly higher in all subscales of the MFI-20 compared to controls but similar to FM. The ICCs were satisfactory, ranging from 0.66 for general fatigue to 0.85 for the total score of MFI-20. All subscales correlated significantly to VAS for global fatigue, general fatigue showing the highest correlation (r(s) = 0.70). The estimated number of hours of sleep/day was significantly associated with many of the fatigue dimensions. All five subscales of the MFI-20 were inversely associated with diastolic blood pressure (BP) and two with systolic BP.

    CONCLUSIONS: The MFI-20 was found to be a reliable and valid tool for the measurement of fatigue in primary SS. High levels of fatigue were correlated with low BP, suggesting an associated involvement of the autonomic nervous system.

  • 310.
    Forsblad-d'Elia, Helena
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Carlsten, Hans
    Bone mineral density by digital X-ray radiogrammetry is strongly decreased and associated with joint destruction in long-standing rheumatoid arthritis: a cross-sectional study.2011Ingår i: BMC musculoskeletal disorders, ISSN 1471-2474, Vol. 12, s. 242-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The aims were to explore bone mineral density (BMD) by digital X-ray radiogrammetry (DXR) in postmenopausal women with long-lasting rheumatoid arthritis (RA) in relation to dual x-ray absorptiometry (DXA)-BMD, joint destruction by conventional radiographs and disease related variables in a cross-sectional study.

    METHODS: Seventy-five postmenopausal women with RA were examined by DXA measuring DXA-BMD of the forearm, total hip and lumbar spine, by scoring joint destruction on plain radiographs by the method of Larsen and by DXR-BMD in metacarpals two to four. The DXR-BMD results of the RA women were compared with an age and sex-matched reference database. A function of DXR-BMD in relation to age and disease duration was created. Associations were investigated by bivariate and multiple linear regression analyses.

    RESULTS: DXR-BMD was strongly decreased in RA patients compared to the reference database (p < 0.001). Calculations showed that DXR-BMD was not markedly influenced the first years after diagnosis of RA, but between approximately 5-10 years of disease there was a steep decline in DXR-BMD which subsequently levelled off. In multiple regression analyses disease duration, CRP and DXR-BMD were independent variables associated with Larsen score (R2= 0.64). Larsen score and BMD forearm were independent determinants of DXR-BMD (R2 = 0.79).

    CONCLUSIONS: DXR-BMD was strongly reduced and associated with both Larsen score and DXA-BMD forearm in these postmenopausal women with RA implying that DXR-BMD is a technique that reflects both the erosive process and bone loss adjacent to affected joints.

  • 311.
    Forsblad-d'Elia, Helena
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Carlsten, Hans
    Hormone replacement therapy in postmenopausal women with rheumatoid arthritis stabilises bone mineral density by digital x-ray radiogrammetry in a randomised controlled trial.2011Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 70, nr 6, s. 1167-8Artikel i tidskrift (Refereegranskat)
  • 312.
    Forsblad-d'Elia, Helena
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Carlsten, Hans
    Labrie, Fernand
    Konttinen, Yrjö T
    Ohlsson, Claes
    Low serum levels of sex steroids are associated with disease characteristics in primary Sjogren's syndrome; supplementation with dehydroepiandrosterone restores the concentrations.2009Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, nr 6, s. 2044-51Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Serum levels of the sex steroid prohormones dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) decline upon aging and are reduced in primary Sjogren's syndrome.

    OBJECTIVE: Our aim was to investigate: 1) effects of 50 mg oral DHEA/day on changes in serum levels of DHEA and 12 of its metabolites; 2) relationships between steroid levels and disease characteristics; and 3) whether these parameters were influenced by DHEA.

    DESIGN: Twenty-three postmenopausal women with primary Sjogren's syndrome and subnormal levels of DHEA-S were included in a randomized, 9-month, controlled, double blind crossover study. Liquid chromatography/mass spectrometry (MS)/MS and gas chromatography/MS were used to measure the sex steroids. Anti-SS-A/Ro and/or anti-SS-B/La, salivary gland focus score, salivary flow rates, dry mouth and eye symptoms, and routine laboratory tests were assessed.

    RESULTS: Baseline erythrocyte sedimentation rate was inversely correlated with testosterone (Testo), dihydrotestosterone, and DHEA-S (rs = -0.42, -0.45, and -0.58, respectively). Dry mouth symptoms correlated with low Testo and androstenedione, whereas dry eyes correlated with low estrogens, most strongly estrone (rs = -0.63). Presence of anti-SS-A and/or anti-SS-B was independently associated with low estradiol (area under the receiver operating characteristic curve, 0.82). All metabolites increased during DHEA but not during placebo. The relative increases were less for estrogens and Testo compared to dihydrotestosterone and glucuronidated androgen metabolites. Dry mouth symptoms decreased during DHEA therapy.

    CONCLUSIONS: Disease manifestations in primary Sjogren's syndrome were associated with low sex hormone levels, dry mouth symptoms with low androgens, and dry eyes with low estrogens. Exogenous DHEA was preferentially transformed into androgens rather than into estrogens.

  • 313.
    Forsblad-d'Elia, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Law, Lucy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Beckman Rehnman, Jeannette
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Deminger, A.
    Klingberg, E.
    Jacobsson, L. T. H.
    High disease activity, reduced physical function, long disease duration, fatigue and living without a partner are factors related to worse health related quality of life in ankylosing spondylitis2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 347-347Artikel i tidskrift (Övrigt vetenskapligt)
  • 314.
    Forsblad-d'Elia, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Law, Lucy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Bengtsson, Karin
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Educed strain and increased stiffness of common carotid arteries in patients with ankylogin spondylitis2019Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, s. 1241-1241Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Ankylosing spondylitis (AS) is associated with an increased risk of cardiovascular disease (CVD) which also contributes to the increased mortality observed in AS. It is therefore important to develop non-invasive, accurate methods for early detection of atherosclerotic vascular changes. Studies, in other populations, have demonstrated associations between arterial stiffness and atherosclerotic burden and incident cardiovascular events. The arterial stiffness can be examined by ultrasound providing the β stiffness index that evaluates mechanical deformation properties. Technological advancements in ultrasound have developed a method assessing strain, using speckle tracking technique, which measures deformation mechanics in more dimensions. The speckle tracking method assessing arterial wall motion might permit earlier detection of subclinical CVD.

    Objectives: To study, for the first time, bilateral common carotid arterial (CCA) circumferential strain and β stiffness index in patients with AS and 1) compare the results with age and sex-matched controls and 2) explore relationships between circumferential strain and β stiffness index with disease activity, physical function and traditional risk factors for CVD in patients with AS.

    Methods: A cohort of 149 patients with AS from Northern Sweden (Modif NY, mean age 55.3±11.2 years, 102(68.5%) men, 146(98%) HLAB27) were assessed with spinal radiographs for mSASSS, clinical examination and BASMI, BASFI, ASDAS-CRP and BASDAI. Forty-six patients with AS (50.4±8.7 years, 31(67%) men) and 46 age- and sex-matched controls (49.8±9.2 years, 31(67%) men) with no known hypertension, diabetes or previous CV events were compared. Bilateral CCA ultrasound was carried out on all patients and controls. The circumferential systolic strain was measured and the β stiffness index was calculated. To analyze factors associated with strain and β stiffness index univariate and standard multivariable linear regression analyses were used. Variables with a univariate p-value ≤ 0.1 were considered for the multivariable models. For dichotomous variables, yes was coded 1 and no was coded 0.

    Results: The mean strain was significantly lower in AS patients compared with controls, 7.9±2.6% vs 10.3±1.9%, p<0.001 and the mean β stiffness index was significantly higher in AS compared to controls, 13.1±1.6 mmHg/mm vs 12.3±1.3 mmHg/mm, p=0.018.

  • 315.
    Franck-Larsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gastrointestinal Manifestations and Pathophysiological Mechanisms in Systemic Sclerosis2010Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Systemic sclerosis (SSc) is a rare systemic, autoimmune disease characterized by vascular changes and fibrosis of the skin and internal organs.

    Patients with SSc more frequently than healthy controls reported upper gastrointestinal (GI) symptoms, which was more abundant in the diffuse cutaneous form (dcSSc) of the disease than in the limited (lcSSc). One-third of a population-based cohort of 79 SSc patients reported faecal incontinence, compared to 11% in 158 healthy matched controls (p<0.001), and this symptom negatively influenced general well-being and social life. Impaired rectal sensibility, rectal bleeding, irritable bowel syndrome-like symptoms, abdominal pain, the need for manual assistance at defecation, and the use of oral laxatives were more common in patients than in controls. SSc patients reported lower scores in both physical and mental scales of the SF-36 questionnaire than controls, indicating worse health-related quality of life.

    Gastric emptying was slower in patients than in controls, and a higher prevalence of delayed gastric emptying in patients with dcSSc indicated more severe GI tract involvement than in lcSSc. Electrogastrographic recordings did not correlate to gastric emptying results, indicating factors other than defective myoelectric signals contributed to disturbed gastric function.

    SSc patients with faecal incontinence had lower anal squeeze pressures than patients without this symptom. Only patients with faecal incontinence had ultrasonographic abnormalities in the internal and external anal sphincters, and absence of the rectoanal inhibitory reflex. Thus, faecal incontinence in SSc patients may depend on both neurogenic and structural mechanisms. A discrete increase in fibre density observed in a majority of SSc patients might have implications from a disease mechanistic perspective.

    Sera from 47% of 70 SSc patients had the capacity to induce interferon (IFN)-α, production which correlated to the presence of anti-RNP and anti-SSA autoantibodies. Increased serum levels of IFN-inducible protein were associated with vascular manifestations, and increased serum levels of IFN-α with digital ulcers. Increased serum levels of monocyte chemoattractant protein-1 or IFN-α were associated with lung fibrosis. An activated type I IFN system previously observed in several other systemic autoimmune diseases is also present in SSc and may contribute to vascular pathology and the pro-fibrotic process.

  • 316.
    Franck-Larsson, Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Edebol Eeg-Olofsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Axelson, Hans W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Rönnblom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Physiological and structural anorectal abnormalities in patients with systemic sclerosis and fecal incontinence2014Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, nr 9, s. 1073-1083Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    Fecal incontinence is common in systemic sclerosis (SSc), but the underlying mechanisms are not fully understood. The objectives of this study were to characterize anorectal physiological and morphological defects in SSc patients and to correlate the results with incontinence symptoms.

    Materials and methods

    Twenty-five SSc patients underwent anorectal neurophysiological investigations, anal manometry, and ultrasound.

    Results

    Eleven patients (44%) reported incontinence to solid or liquid feces, but no patient reported diarrhea. Increased fiber density (FD) was recorded in 78% of patients with and in 86% of patients without fecal incontinence not significant (NS). Incontinent patients had lower squeeze pressure (SP; median 49.5 mm Hg) in the high-pressure zone (HPZ) than continent patients (median 72 mm Hg; p = 0.01). In two of the incontinent patients, sonographic abnormalities of the internal anal sphincter (IAS) and the external anal sphincter (EAS) were present, whereas in another two patients isolated IAS abnormalities were seen. These four individuals had lower resting pressure at 1 cm and in the HPZ, and lower SP at 2 cm than patients with normal anorectal sonographic findings (p < 0.05).

    Conclusion

    Lower voluntary SP in incontinent patients and EAS sonographic abnormalities only in patients with incontinence suggest that the EAS is more important in maintaining fecal continence in SSc patients than has previously been reported. The finding of increased FD in most patients further supports involvement of the EAS function in SSc and could indicate previous nerve injury with consequent incomplete reinnervation.

  • 317.
    Franck-Larsson, Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Edebol-Eeg Olofsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Axelson, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Rönnblom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Physiological and structural abnormalities in patients with systemic sclerosis and faecal incontinenceManuskript (preprint) (Övrigt vetenskapligt)
  • 318.
    Franklin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Extra-articular manifestations in early rheumatoid arthritis - Frequency and predisposing factors2017Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 319.
    Fredlund, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Svedin, Carl Göran
    Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barnafrid. Linköpings universitet, Medicinska fakulteten.
    Pribe, Gisela
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barnafrid. Linköpings universitet, Medicinska fakulteten.
    Jonsson, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barnafrid. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Wadsby, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Self-reported frequency of sex as self-injury (SASI) in a national study of Swedish adolescents and association to sociodemographic factors, sexual behaviors, abuse and mental health2017Ingår i: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 11, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sex as self-injury has become a concept in Swedish society; however it is a largely unexplored area of research, not yet conceptualized and far from accepted in the research field. The use of sex as a way of affect regulation is known in the literature and has, in interviews with young women who sell sex, been compared to direct self-injury, such as cutting or burning the skin. The aim of this study was to investigate the self-reported frequency of sex as self-injury and the association to sociodemographic factors, sexual orientation, voluntary sexual experiences, sexual risk-taking behaviors, sexual, physical and mental abuse, trauma symptoms, healthcare for psychiatric disorders and non-suicidal self-injury.

  • 320. Fredricson, Adrian Salinas
    et al.
    Khodabandehlou, Farid
    Weiner, Carina Krüger
    Naimi-Akbar, Aron
    Adami, Johanna
    Sophiahemmet Högskola.
    Rosén, Annika
    Are there early signs that predict development of temporomandibular joint disease?2018Ingår i: Journal of Oral Science, ISSN 1343-4934, E-ISSN 1880-4926, Vol. 60, nr 2, s. 194-200Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Temporomandibular joint disorders (TMJD) involve orofacial pain and functional limitations that may limit important daily activities such as chewing and speaking. This observational case-control study attempted to identify factors associated with TMJD development, particularly inflammation. The study participants were patients treated at Karolinska University Hospital, Stockholm, Sweden. The cases were patients who received a diagnosis of TMJD, chronic closed lock, or painful clicking and were treated surgically during the period from 2007 through 2011. The control group was randomly selected from among patients who had undergone tooth extraction and was matched by age and sex. A total of 146 cases and 151 controls were included in the analyses. The response rate was 55.3% for the case group and 21.8% for the control group. The male:female ratio for patients with TMJD was 1:4.4. TMJD was significantly associated with pneumonia (odds ratio [OR], 2.1), asthma (OR, 2.1), allergies (OR, 1.8), headache (OR, 3.1), general joint hypermobility (OR, 3.8), orofacial trauma (OR, 3.9), rheumatism (OR, 2.5), and orthodontic treatment (OR, 2.4) (P < 0.05 for all outcomes). In conclusion, autoimmune diseases and inflammatory conditions are associated with increased risk of TMJD. Moreover, certain lung disorders may predict subsequent development of TMJD.

  • 321. Frisell, T.
    et al.
    Baecklund, E.
    Bengtsson, K.
    Di Giuseppe, D.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Askling, J.
    Confounding by indication will make NON-TNFI BDMARDS appear more harmful than TNFI bdmards - a nationwide study of channeling in sweden 2010-20142017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 134-135Artikel i tidskrift (Övrigt vetenskapligt)
  • 322.
    Frisell, T.
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Bengtsson, K.
    Sahlgrens Acad, Gothenburg, Sweden..
    Di Giuseppe, D.
    Karolinska Inst, Stockholm, Sweden..
    Forsblad-d'Elia, H.
    Umea Univ, Umea, Sweden..
    Askling, J.
    Karolinska Inst, Stockholm, Sweden..
    Confounding By Indication Will Make Non-Tnfi Bdmards Appear More Harmful Than Tnfi Bdmards A Nationwide Study Of Channeling In Sweden 2010-20142017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 134-135Artikel i tidskrift (Övrigt vetenskapligt)
  • 323. Frisell, Thomas
    et al.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Bengtsson, Karin
    Di Giuseppe, Daniela
    Forsblad-d'Elia, Helena
    Askling, Johan
    Patient characteristics influence the choice of biological drug in RA, and will make non-TNFi biologics appear more harmful than TNFi biologics2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, nr 5, s. 650-657Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: With the wide range of biological disease-modifying anti-rheumatic drugs (bDMARDs) available for treating rheumatoid arthritis (RA), and limited evidence to guide the choice for individual patients, we wished to evaluate whether patient characteristics influence the choice of bDMARD in clinical practice, and to quantify the extent to which this would bias direct comparisons of treatment outcome.

    Methods: Register-based study of all Swedish patients with RA initiating necrosis factor inhibitor (TNFi), rituximab, abatacept or tocilizumab in 2011–2015 as their first bDMARD (n=6481), or after switch from TNFi as first bDMARD (n=2829). Group differences in demographics, clinical characteristics and medical history were assessed in multivariable regression models. Predicted differences in safety and treatment outcomes were calculated as a function of patient characteristics, through regression modelling based on observed outcomes among patients with RA starting bDMARDs 2006–2010.

    Results: Patients starting non-TNFi were older than those starting TNFi, had lower socioeconomic status, higher disease activity and higher burden of diseases including malignancy, serious infections and diabetes. Differences were most pronounced at first bDMARD initiation. These factors were linked to treatment outcome independent of therapy, yielding worse apparent safety and effectiveness for non-TNFi biologics, most extreme for rituximab. Standardising to the age/sex distribution of the TNFi group reduced differences considerably.

    Conclusions: There was significant channelling of older and less healthy patients with RA to non-TNFi bDMARDs, in particular as first bDMARD. Whether this channelling represents a maximised benefit/risk ratio is unclear. Unless differences in age, medical history and disease activity are accounted for, they will substantially confound non-randomised comparative studies of available bDMARDs’ safety and effectiveness.

  • 324. Frisell, Thomas
    et al.
    Baecklund, Eva
    Bengtsson, Karin
    Di Giuseppe, Daniela
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Askling, Johan
    Patient characteristics influence the choice of biological drug in RA, and will make non-TNFi biologics appear more harmful than TNFi biologics2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, nr 5, s. 650-657Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives With the wide range of biological disease-modifying anti-rheumatic drugs (bDMARDs) available for treating rheumatoid arthritis (RA), and limited evidence to guide the choice for individual patients, we wished to evaluate whether patient characteristics influence the choice of bDMARD in clinical practice, and to quantify the extent to which this would bias direct comparisons of treatment outcome. Methods Register-based study of all Swedish patients with RA initiating necrosis factor inhibitor (TNFi), rituximab, abatacept or tocilizumab in 2011-2015 as their first bDMARD (n=6481), or after switch from TNFi as first bDMARD (n=2829). Group differences in demographics, clinical characteristics and medical history were assessed in multivariable regression models. Predicted differences in safety and treatment outcomes were calculated as a function of patient characteristics, through regression modelling based on observed outcomes among patients with RA starting bDMARDs 2006-2010. Results Patients starting non-TNFi were older than those starting TNFi, had lower socioeconomic status, higher disease activity and higher burden of diseases including malignancy, serious infections and diabetes. Differences were most pronounced at first bDMARD initiation. These factors were linked to treatment outcome independent of therapy, yielding worse apparent safety and effectiveness for non-TNFi biologics, most extreme for rituximab. Standardising to the age/sex distribution of the TNFi group reduced differences considerably. Conclusions There was significant channelling of older and less healthy patients with RA to non-TNFi bDMARDs, in particular as first bDMARD. Whether this channelling represents a maximised benefit/risk ratio is unclear. Unless differences in age, medical history and disease activity are accounted for, they will substantially confound non-randomised comparative studies of available bDMARDs' safety and effectiveness.

  • 325.
    Frodlund, M.
    et al.
    Linkoping Univ, Dept Clin & Expt Med, Div Neuro & Inflammat Sci, Linkoping, Sweden.
    Reid, Sarah
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wettero, J.
    Linkoping Univ, Dept Clin & Expt Med, Div Neuro & Inflammat Sci, Linkoping, Sweden.
    Dahlstrom, O.
    Linkoping Univ, Swedish Inst Disabil Res, Dept Behav Sci & Learning, Linkoping, Sweden.
    Sjowall, C.
    Linkoping Univ, Dept Clin & Expt Med, Div Neuro & Inflammat Sci, Linkoping, Sweden.
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    The majority of Swedish systemic lupus erythematosus patients are still affected by irreversible organ impairment: factors related to damage accrual in two regional cohorts2019Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 28, nr 10, s. 1261-1272, artikel-id UNSP 0961203319860198Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Although the survival of patients with systemic lupus erythematosus (SLE) has improved, irreversible organ damage remains a critical concern. We aimed to characterize damage accrual and its clinical associations and causes of death in Swedish patients. Methods Accumulation of damage was evaluated in 543 consecutively recruited and well-characterized cases during 1998-2017. The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index (SDI) was used to estimate damage. Results Organ damage (SDI >= 1) was observed in 59%, and extensive damage (SDI >= 3) in 25% of cases. SDI >= 1 was significantly associated with higher age at onset, SLE duration, the number of fulfilled SLICC criteria, neurologic disorder, antiphospholipid antibody syndrome (APS), hypertension, hyperlipidemia, depression and secondary Sjogren's syndrome (SS). In addition, SDI >= 3 was associated with serositis, renal and haematological disorders and interstitial lung disease. A multiple regression model identified not only well-known risk factors like APS, antihypertensives and corticosteroids, but pericarditis, haemolytic anaemia, lymphopenia and myositis as being linked to SDI. Malignancy, infection and cardiovascular disease were the leading causes of death. Conclusions After a mean SLE duration of 17 years, the majority of today's Swedish SLE patients have accrued damage. We confirm previous observations and report some novel findings regarding disease phenotypes and damage accrual.

  • 326.
    Frodlund, M.
    et al.
    Linkoping Univ, Dept Clin & Expt Med, Div Neuro & Inflammat Sci, Linkoping, Sweden.
    Vikerfors, A.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Unit Rheumatol, Stockholm, Sweden.
    Elvin, K.
    Karolinska Inst, Dept Clin Immunol & Transfus Med, Div Clin Immunol, Stockholm, Sweden.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Svenungsson, E.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Unit Rheumatol, Stockholm, Sweden.
    Sjowall, C.
    Linkoping Univ, Dept Clin & Expt Med, Div Neuro & Inflammat Sci, Linkoping, Sweden.
    Immunoglobulin A anti-phospholipid antibodies in Swedish cases with systemic lupus erythematosus: associations with disease phenotypes, vascular events, and damage accrual2018Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, s. 48-48Artikel i tidskrift (Övrigt vetenskapligt)
  • 327.
    Frodlund, M.
    et al.
    Linkoping Univ, Div Neuro & Inflammat Sci, Dept Clin & Expt Med, Linkoping, Sweden.
    Vikerfors, A.
    Swedish Med Prod Agcy, SE-75103 Uppsala, Sweden;Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Rheumatol, Stockholm, Sweden.
    Grosso, G.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Rheumatol, Stockholm, Sweden.
    Skogh, T.
    Linkoping Univ, Div Neuro & Inflammat Sci, Dept Clin & Expt Med, Linkoping, Sweden.
    Wetterö, J.
    Linkoping Univ, Div Neuro & Inflammat Sci, Dept Clin & Expt Med, Linkoping, Sweden.
    Elvin, K.
    Karolinska Inst, Dept Clin Immunol & Transfus Med, Unit Clin Immunol, Stockholm, Sweden.
    Gunnarsson, I.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Rheumatol, Stockholm, Sweden.
    Kastbom, A.
    Linkoping Univ, Div Neuro & Inflammat Sci, Dept Clin & Expt Med, Linkoping, Sweden.
    Dahlström, Ö.
    Linkoping Univ, Swedish Inst Disabil Res, Dept Behav Sci & Learning, Linkoping, Sweden.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Svenungsson, E.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Rheumatol, Stockholm, Sweden.
    Sjöwall, C.
    Linkoping Univ, Div Neuro & Inflammat Sci, Dept Clin & Expt Med, Linkoping, Sweden.
    Immunoglobulin A anti-phospholipid antibodies in Swedish cases of systemic lupus erythematosus: associations with disease phenotypes, vascular events and damage accrual2018Ingår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 194, nr 1, s. 27-38Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-(2)-glycoprotein-I (anti-(2)GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-(2)GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97. Patients with rheumatoid arthritis (n=100), primary Sjogren's syndrome (n=50) and blood donors (n=507) served as controls. Anti-phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays detecting aCL/anti-(2)GPI. Seventy-six (14%) SLE cases fulfilled the Sydney APS-criteria, and 1 aCL/anti-(2)GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%) lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-(2)GPI, 34 (6%) being seronegative regarding IgG/IgM anti-(2)GPI. Six (1%) had APS manifestations but were seropositive regarding IgA-aCL and/or IgA anti-(2)GPI in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were associated with most APS-related events and organ damage. Exclusive IgA anti-(2)GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR)=021, 95% confidence interval (CI)=006-072) and photosensitivity (OR=019, 95% CI=005-072). Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA.

  • 328.
    Frodlund, Martina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Dahlström, Örjan
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten.
    Kastbom, Alf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Associations between antinuclear antibody staining patterns and clinical features of systemic lupus erythematosus: analysis of a regional Swedish register2013Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 3, s. 1-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective Antinuclear antibody (ANA) analysis by immunofluorescence (IF) microscopy remains a diagnostic hallmark of systemic lupus erythematosus (SLE). The clinical relevance of ANA fine-specificities in SLE has been addressed repeatedly, whereas studies on IF-ANA staining patterns in relation to disease manifestations are very scarce. This study was performed to elucidate whether different staining patterns associate with distinct SLE phenotypes.

    Design Observational cohort study.

    Setting One university hospital rheumatology unit in Sweden.

    Participants The study population consisted of 222 cases (89% women; 93% Caucasians), where of 178 met ≥4/11 of the 1982 American College of Rheumatology (ACR-82) criteria. The remaining 20% had an SLE diagnosis based on positive IF-ANA (HEp-2 cells) and ≥2 typical organ manifestations at the time of diagnosis (Fries’ criteria).

    Outcome measures The IF-ANA staining patterns homogenous (H-ANA), speckled (S-ANA), combined homogenous and speckled (HS-ANA), centromeric (C-ANA), nucleolar (N-ANA)±other patterns and other nuclear patterns (oANA) were related to disease manifestations and laboratory measures. Antigen-specificities were also considered regarding double-stranded DNA (Crithidia luciliae) and the following extractable nuclear antigens: Ro/SSA, La/SSB, Smith antigen (Sm), small nuclear RNP (snRNP), Scl-70 and Jo-1 (immunodiffusion and/or line-blot technique).

    Results 54% of the patients with SLE displayed H-ANA, 22% S-ANA, 11% HS-ANA, 9% N-ANA, 1% C-ANA, 2% oANA and 1% were never IF-ANA positive. Staining patterns among patients meeting Fries’ criteria alone did not differ from those fulfilling ACR-82. H-ANA was significantly associated with the 10th criterion according to ACR-82 (‘immunological disorder’). S-ANA was inversely associated with arthritis, ‘immunological disorder’ and signs of organ damage.

    Conclusions H-ANA is the dominant IF-ANA pattern among Swedish patients with SLE, and was found to associate with ‘immunological disorder’ according to ACR-82. The second most common pattern, S-ANA, associated negatively with arthritis and organ damage.

  • 329.
    Frodlund, Martina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Reid, S.
    Uppsala Univ, Sweden.
    Wetterö, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Dahlström, Örjan
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Psykologi. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV).
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Leonard, D.
    Uppsala Univ, Sweden.
    The majority of Swedish systemic lupus erythematosus patients are still affected by irreversible organ impairment: factors related to damage accrual in two regional cohorts2019Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, artikel-id UNSP 0961203319860198Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Although the survival of patients with systemic lupus erythematosus (SLE) has improved, irreversible organ damage remains a critical concern. We aimed to characterize damage accrual and its clinical associations and causes of death in Swedish patients. Methods Accumulation of damage was evaluated in 543 consecutively recruited and well-characterized cases during 1998-2017. The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index (SDI) was used to estimate damage. Results Organ damage (SDI amp;gt;= 1) was observed in 59%, and extensive damage (SDI amp;gt;= 3) in 25% of cases. SDI amp;gt;= 1 was significantly associated with higher age at onset, SLE duration, the number of fulfilled SLICC criteria, neurologic disorder, antiphospholipid antibody syndrome (APS), hypertension, hyperlipidemia, depression and secondary Sjogrens syndrome (SS). In addition, SDI amp;gt;= 3 was associated with serositis, renal and haematological disorders and interstitial lung disease. A multiple regression model identified not only well-known risk factors like APS, antihypertensives and corticosteroids, but pericarditis, haemolytic anaemia, lymphopenia and myositis as being linked to SDI. Malignancy, infection and cardiovascular disease were the leading causes of death. Conclusions After a mean SLE duration of 17 years, the majority of todays Swedish SLE patients have accrued damage. We confirm previous observations and report some novel findings regarding disease phenotypes and damage accrual.

  • 330. Frostegård, J.
    et al.
    Hellström, Cecilia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Frostegård, A. G.
    Ajeganova, S.
    Autoantibody profiling reveals four protein candidate autoantigens associated with systemic lupus erythematosus2018Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 27, nr 10, s. 1670-1678Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives In systemic lupus erythematosus (SLE) there are typically many autoantibodies. The disease heterogeneity could be better understood with discovery of phenotype-specific antigens targeted by autoantibodies. We here aimed to identify novel autoantigens potentially related to SLE disease and a major complication, atherosclerosis. Methods Antigen microarrays were used to profile IgG autoantibody reactivity against 77 protein fragments (20-140 amino acids (aa) long, median 89 aa) produced within the Human Protein Atlas project, in serum samples from SLE patients (n=107) and age- and sex-matched population-based controls (n=107). Common carotid intima-media thickness, plaque occurrence and echogenicity were determined by B-mode ultrasound. Results We determined significant differences between patients and controls in IgG reactivity against four proteins. In patients compared to controls, there was an increase of IgG reactivity against zinc finger protein 688 (ZNF688), early B cell factor 2 (EBF2), crystallin, alpha B (CRYAB) and tumor necrosis factor receptor superfamily member 13C (TNFRSF13C). Of these four antigens, only anti-ZNF688 was associated with carotid atherosclerosis (plaque occurrence) and vulnerable plaques in SLE. There was a weak association between anti-EBF2 and SLE disease activity but no significant associations were determined for other measured IgG reactivity. Conclusions In this discovery screening we here demonstrate new candidate autoantigens with differential reactivity (reflecting autoantibody levels) in SLE patients and in controls and in relation to atherosclerosis in SLE.

  • 331. Gabay, Cem
    et al.
    Emery, Paul
    van Vollenhoven, Ronald
    Dikranian, Ara
    Alten, Rieke
    Pavelka, Karel
    Klearman, Micki
    Musselman, David
    Agarwal, Sunil
    Green, Jennifer
    Kavanaugh, Arthur
    Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial.2013Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 381, nr 9877Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Roughly a third of patients with rheumatoid arthritis treated with biological treatments receive them as monotherapy. Tocilizumab--an inhibitor of interleukin 6 receptor signalling--has been studied as monotherapy in several clinical trials. We assessed the efficacy and safety of tocilizumab monotherapy compared with adalimumab monotherapy for patients with rheumatoid arthritis.

    METHODS: We did this randomised, double-blind, parallel-group, phase 4 superiority study in 76 centres in 15 countries in North and South America, Australasia, and Europe. We enrolled patients who were aged at least 18 years, had severe rheumatoid arthritis for 6 months or more, and were intolerant to methotrexate or were inappropriate for continued methotrexate treatment. Patients were randomly assigned (1:1; block size of four) to receive tocilizumab 8 mg per kg bodyweight intravenously every 4 weeks plus placebo subcutaneously every 2 weeks or adalimumab 40 mg subcutaneously every 2 weeks plus placebo intravenously every 4 weeks for 24 weeks. Investigators, patients, and sponsor personnel were masked to assignment. The primary endpoint was change in disease activity score using 28 joints (DAS28) from baseline to week 24. This trial is registered with ClinicalTrials.gov, number NCT01119859.

    FINDINGS: We screened 452 patients and enrolled 326 patients. The intention-to-treat population contained 325 patients (163 assigned to tocilizumab, 162 assigned to adalimumab). Week 24 mean change from baseline in DAS28 was significantly greater in the tocilizumab group (-3·3) than in the adalimumab group (-1·8) patients (difference -1·5, 95% CI -1·8 to -1·1; p<0·0001). 16 of 162 (10%) patients in the adalimumab group versus 19 of 162 (12%) in the tocilizumab group had serious adverse events. More patients in the tocilizumab group than in the adalimumab group had increased LDL-cholesterol, increased alanine aminotransferase concentrations, and reduced platelet and neutrophil counts.

    INTERPRETATION: Tocilizumab monotherapy was superior to adalimumab monotherapy for reduction of signs and symptoms of rheumatoid arthritis in patients for whom methotrexate was deemed inappropriate. The adverse event profiles of tocilizumab and adalimumab were consistent with previous findings.

    FUNDING: F Hoffmann-La Roche.

  • 332. Gabay, Cem
    et al.
    Emery, Paul
    van Vollenhoven, Ronald
    Dikranian, Ara
    Alten, Rieke
    Pavelka, Karel
    Klearman, Micki
    Musselman, David
    Agarwal, Sunil
    Green, Jennifer
    Kavanaugh, Arthur
    Baecklund, Eva
    Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial.2013Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 381, nr 9877Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Roughly a third of patients with rheumatoid arthritis treated with biological treatments receive them as monotherapy. Tocilizumab--an inhibitor of interleukin 6 receptor signalling--has been studied as monotherapy in several clinical trials. We assessed the efficacy and safety of tocilizumab monotherapy compared with adalimumab monotherapy for patients with rheumatoid arthritis.

    METHODS: We did this randomised, double-blind, parallel-group, phase 4 superiority study in 76 centres in 15 countries in North and South America, Australasia, and Europe. We enrolled patients who were aged at least 18 years, had severe rheumatoid arthritis for 6 months or more, and were intolerant to methotrexate or were inappropriate for continued methotrexate treatment. Patients were randomly assigned (1:1; block size of four) to receive tocilizumab 8 mg per kg bodyweight intravenously every 4 weeks plus placebo subcutaneously every 2 weeks or adalimumab 40 mg subcutaneously every 2 weeks plus placebo intravenously every 4 weeks for 24 weeks. Investigators, patients, and sponsor personnel were masked to assignment. The primary endpoint was change in disease activity score using 28 joints (DAS28) from baseline to week 24. This trial is registered with ClinicalTrials.gov, number NCT01119859.

    FINDINGS: We screened 452 patients and enrolled 326 patients. The intention-to-treat population contained 325 patients (163 assigned to tocilizumab, 162 assigned to adalimumab). Week 24 mean change from baseline in DAS28 was significantly greater in the tocilizumab group (-3·3) than in the adalimumab group (-1·8) patients (difference -1·5, 95% CI -1·8 to -1·1; p<0·0001). 16 of 162 (10%) patients in the adalimumab group versus 19 of 162 (12%) in the tocilizumab group had serious adverse events. More patients in the tocilizumab group than in the adalimumab group had increased LDL-cholesterol, increased alanine aminotransferase concentrations, and reduced platelet and neutrophil counts.

    INTERPRETATION: Tocilizumab monotherapy was superior to adalimumab monotherapy for reduction of signs and symptoms of rheumatoid arthritis in patients for whom methotrexate was deemed inappropriate. The adverse event profiles of tocilizumab and adalimumab were consistent with previous findings.

    FUNDING: F Hoffmann-La Roche.

  • 333.
    Gallo, Lina Marcela Diaz
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Dept Med,Rheumatol Unit, Stockholm, Sweden..
    Lundstrom, Emeli
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Dept Med,Rheumatol Unit, Stockholm, Sweden..
    Oke, Vilija
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Dept Med,Rheumatol Unit, Stockholm, Sweden..
    Elvin, Kerstin
    Karolinska Univ Hosp, Karolinska Inst, Dept Clin Immunol & Transfus Med, Unit Clin Immunol,Dept Med Solna,Rheumatol Unit, Stockholm, Sweden..
    Wu, Yee Ling
    Nationwide Childrens Hosp, Res Inst, Columbus, OH USA.;Ohio State Univ, Columbus, OH 43210 USA..
    Gustafsson, Johanna
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Dept Med,Rheumatol Unit, Stockholm, Sweden..
    Jonsen, Andreas
    Lund Univ, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Zickert, Agneta
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Bengtsson, Anders A.
    Lund Univ, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Sandling, Johanna K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Dept Med,Rheumatol Unit, Stockholm, Sweden..
    Yu, Chack-Yung
    Nationwide Childrens Hosp, Res Inst, Ctr Mol & Human Genet, Columbus, OH USA..
    Padyukov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    SLE Comprises Four Immune-Phenotypes, Which Differ Regarding HLA-DRB1 and Clinical Associations2017Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, nr S10, artikel-id 1675Artikel i tidskrift (Övrigt vetenskapligt)
  • 334.
    Gateva, Vesela
    et al.
    Immunology Biomarkers Group, Genentech, South San Francisco, California, USA.
    Sandling, Johanna K
    Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Hom, Geoff
    Immunology Biomarkers Group, Genentech, South San Francisco, California, USA.
    Taylor, Kimberly E
    Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco, California, USA.
    Chung, Sharon A
    Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco, California, USA.
    Sun, Xin
    Immunology Biomarkers Group, Genentech, South San Francisco, California, USA.
    Ortmann, Ward
    Immunology Biomarkers Group, Genentech, South San Francisco, California, USA.
    Kosoy, Roman
    Rowe Program in Genetics, University of California at Davis, Davis, California, USA.
    Ferreira, Ricardo C
    Immunology Biomarkers Group, Genentech, South San Francisco, California, USA.
    Nordmark, Gunnel
    Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Gunnarsson, Iva
    Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Svenungsson, Elisabet
    Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Padyukov, Leonid
    Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Sturfelt, Gunnar
    Section of Rheumatology, Department of Clinical Sciences, Lund University Hospital, Lund, Sweden.
    Jönsen, Andreas
    Section of Rheumatology, Department of Clinical Sciences, Lund University Hospital, Lund, Sweden.
    Bengtsson, Anders A
    Section of Rheumatology, Department of Clinical Sciences, Lund University Hospital, Lund, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Baechler, Emily C
    Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
    Brown, Elizabeth E
    University of Alabama at Birmingham, Birmingham, Alabama, USA.
    Alarcón, Graciela S
    University of Alabama at Birmingham, Birmingham, Alabama, USA.
    Edberg, Jeffrey C
    University of Alabama at Birmingham, Birmingham, Alabama, USA.
    Ramsey-Goldman, Rosalind
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
    McGwin, Gerald
    University of Alabama at Birmingham, Birmingham, Alabama, USA.
    Reveille, John D
    University of Texas–Houston Health Science Center, Houston, Texas, USA.
    Vilá, Luis M
    University of Puerto Rico Medical Science Campus, San Juan, Puerto Rico.
    Kimberly, Robert P
    University of Alabama at Birmingham, Birmingham, Alabama, USA.
    Manzi, Susan
    University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
    Petri, Michelle A
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
    Lee, Annette
    The Feinstein Institute for Medical Research, North Shore–Long Island Jewish Health System, Manhasset, New York, USA.
    Gregersen, Peter K
    The Feinstein Institute for Medical Research, North Shore–Long Island Jewish Health System, Manhasset, New York, USA.
    Seldin, Michael F
    Rowe Program in Genetics, University of California at Davis, Davis, California, USA.
    Rönnblom, Lars
    Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Criswell, Lindsey A
    Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco, California, USA.
    Syvänen, Ann-Christine
    Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Behrens, Timothy W
    Immunology Biomarkers Group, Genentech, South San Francisco, California, USA.
    Graham, Robert R
    Immunology Biomarkers Group, Genentech, South San Francisco, California, USA.
    A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.2009Ingår i: Nature genetics, ISSN 1546-1718, Vol. 41, nr 11, s. 1228-1233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.

  • 335.
    Ge, Changrong
    et al.
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Tong, Dongmei
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Southern Medical University, Guangzhou, China..
    Liang, Bibo
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm,Southern Medical University, Guangzhou, China.
    Lönnblom, Erik
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm.
    Schneider, Nadine
    University Hospital Frankfurt Goethe University, Frankfurt, Germany.
    Hagert, Cecilia
    University of Turku, Finland.
    Viljanen, Johan
    Biomedicinskt centrum, Uppsala University, Uppsala, Sweden.
    Ayoglu, Burcu
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Stawikowska, Roma
    Florida Atlantic University, Jupiter, Florida, USA.
    Nilsson, Peter
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Fields, Gregg B
    Florida Atlantic University, Jupiter, Florida, USA.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Kastbom, Alf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Kihlberg, Jan
    Uppsala University, Uppsala, Sweden.
    Burkhardt, Harald
    University Hospital Frankfurt Goethe University, Frankfurt, Germany.
    Dobritzsch, Doreen
    Uppsala University, Uppsala, Sweden.
    Holmdahl, Rikard
    Karolinska Institutet, Stockholm, Sweden; University of Turku, Turku, Finland, Southern Medical University, Guangzhou, China.
    Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage2017Ingår i: JCI insight, ISSN 2379-3708, Vol. 2, nr 13, artikel-id 93688Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis.

  • 336.
    Ge, Changrong
    et al.
    Karolinska Inst, Sweden.
    Xu, Bingze
    Karolinska Inst, Sweden.
    Liang, Bibo
    Karolinska Inst, Sweden; Southern Med Univ, Peoples R China.
    Lonnblom, Erik
    Karolinska Inst, Sweden.
    Lundstrom, Susanna L.
    Karolinska Inst, Sweden.
    Zubarev, Roman A.
    Karolinska Inst, Sweden.
    Ayoglu, Burcu
    KTH Royal Inst Technol, Sweden.
    Nilsson, Peter
    KTH Royal Inst Technol, Sweden.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Kastbom, Alf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Malmstrom, Vivianne
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Klareskog, Lars
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Toes, Rene E. M.
    Leiden Univ, Netherlands.
    Rispens, Theo
    Univ Amsterdam, Netherlands.
    Dobritzsch, Doreen
    Uppsala Univ, Sweden.
    Holmdahl, Rikard
    Karolinska Inst, Sweden; Southern Med Univ, Peoples R China.
    Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies2019Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 71, nr 2, s. 210-221Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. Methods Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. Results Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. Conclusion These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.

  • 337.
    Ge, Changrong
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Xu, Bingze
    Karolinska Inst, Stockholm, Sweden.
    Liang, Bibo
    Karolinska Inst, Stockholm, Sweden;Southern Med Univ, Guangzhou, Guangdong, Peoples R China.
    Lönnblom, Erik
    Karolinska Inst, Stockholm, Sweden.
    Lundström, Susanna L.
    Karolinska Inst, Stockholm, Sweden.
    Zubarev, Roman A.
    Karolinska Inst, Stockholm, Sweden.
    Ayoglu, Burcu
    KTH Royal Inst Technol, Stockholm, Sweden.
    Nilsson, Peter
    KTH Royal Inst Technol, Stockholm, Sweden.
    Skogh, Thomas
    Linkoping Univ, Linkoping, Sweden.
    Kastbom, Alf
    Linkoping Univ, Linkoping, Sweden.
    Malmström, Vivianne
    Karolinska Inst, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Klareskog, Lars
    Karolinska Inst, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Toes, Rene E. M.
    Leiden Univ, Med Ctr, Leiden, Netherlands.
    Rispens, Theo
    Univ Amsterdam, Amsterdam, Netherlands.
    Dobritzsch, Doreen
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Holmdahl, Rikard
    Karolinska Inst, Stockholm, Sweden;Southern Med Univ, Guangzhou, Guangdong, Peoples R China.
    Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies2019Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 71, nr 2, s. 210-221Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA.

    Methods: Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients.

    Results: Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients.

    Conclusion: These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.

  • 338.
    Geenen, Rinie
    et al.
    Univ Utrecht, Dept Psychol, Heidelberglaan 1, NL-3584 CS Utrecht, Netherlands..
    Overman, Cecile L.
    Univ Utrecht, Dept Psychol, Heidelberglaan 1, NL-3584 CS Utrecht, Netherlands..
    Christensen, Robin
    Bispebjerg & Frederiksberg Hosp, Parker Inst, Musculoskeletal Stat Unit, Copenhagen, Denmark.;Odense Univ Hosp, Dept Rheumatol, Odense, Denmark..
    Åsenlöf, Pernilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Capela, Susana
    Hosp Santa Maria, Rheumatol & Metab Bone Dis Dept, Lisbon, Portugal.;Univ Lisbon, Lisbon Acad Med Ctr, Inst Med Mol, Fac Med,Rheumatol Res Unit, Lisbon, Portugal..
    Huisinga, Karen L.
    Virginia Mason Med Ctr, Dept Rheumatol, Seattle, WA 98101 USA..
    Husebo, Mai Elin P.
    Diakonhjemmet Hosp, Norwegian Natl Unit Rehabil Rheumat Patients Spec, NBRR, Oslo, Norway..
    Koke, Albere J. A.
    Maastricht Univ, Dept Rehabil Med, Maastricht, Netherlands..
    Paskins, Zoe
    Keele Univ, Res Inst Primary Care & Hlth Sci, Keele, Staffs, England.;Haywood Hosp, Haywood Acad Rheumatol Ctr, Stoke On Trent, Staffs, England..
    Pitsillidou, Irene A.
    Cyprus League Rheumatism, EULAR Patient Res Partner, Nicosia, Cyprus..
    Savel, Carine
    CHU Clermont Ferrand, Dept Rheumatol, Clermont Ferrand, France..
    Austin, Judith
    Univ Utrecht, Dept Psychol, Heidelberglaan 1, NL-3584 CS Utrecht, Netherlands..
    Hassett, Afton L.
    Univ Michigan, Sch Med, Chron Pain & Fatigue Res Ctr, Dept Anesthesiol,Div Pain Res, Ann Arbor, MI USA..
    Severijns, Guy
    EULAR Social Leagues Patients Representat, Leuven, Belgium..
    Stoffer-Marx, Michaela
    Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, Sect Outcomes Res, Vienna, Austria.;Univ Appl Sci, Dept Hlth Sci, FH Campus Wien, Vienna, Austria..
    Vlaeyen, Johan W. S.
    Univ Leuven, Res Grp Hlth Psychol, Leuven, Belgium.;Maastricht Univ, Fac Psychol & Neurosci, Behav Med Res, Maastricht, Netherlands..
    Fernandez-de-las-Penas, Cesar
    Univ Rey Juan Carlos, Dept Phys Therapy Occupat Therapy Rehabil & Phys, Alcorcon, Spain..
    Ryan, Sarah J.
    Haywood Hosp, Haywood Acad Rheumatol Ctr, Stoke On Trent, Staffs, England..
    Bergman, Stefan
    Univ Gothenburg, Sahlgrenska Acad, Dept Publ Hlth & Community Med, Primary Hlth Care Unit,Inst Med, Gothenburg, Sweden..
    EULAR recommendations for the health professional's approach to pain management in inflammatory arthritis and osteoarthritis2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, nr 6, s. 797-807Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Pain is the predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA) mandating the development of evidence-based recommendations for the health professional's approach to pain management. A multidisciplinary task force including professionals and patient representatives conducted a systematic literature review of systematic reviews to evaluate evidence regarding effects on pain of multiple treatment modalities. Overarching principles and recommendations regarding assessment and pain treatment were specified on the basis of reviewed evidence and expert opinion. From 2914 review studies initially identified, 186 met inclusion criteria. The task force emphasised the importance for the health professional to adopt a patient-centred framework within a biopsychosocial perspective, to have sufficient knowledge of IA and OA pathogenesis, and to be able to differentiate localised and generalised pain. Treatment is guided by scientific evidence and the assessment of patient needs, preferences and priorities; pain characteristics; previous and ongoing pain treatments; inflammation and joint damage; and psychological and other pain-related factors. Pain treatment options typically include education complemented by physical activity and exercise, orthotics, psychological and social interventions, sleep hygiene education, weight management, pharmacological and joint-specific treatment options, or interdisciplinary pain management. Effects on pain were most uniformly positive for physical activity and exercise interventions, and for psychological interventions. Effects on pain for educational interventions, orthotics, weight management and multidisciplinary treatment were shown for particular disease groups. Underpinned by available systematic reviews and meta-analyses, these recommendations enable health professionals to provide knowledgeable pain-management support for people with IA and OA.

  • 339.
    Geijer, Mats
    et al.
    Skane Univ Hosp, Ctr Med Imaging & Physiol, S-22185 Lund, Sweden..
    Lindqvist, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Husmark, Tomas
    Falu Lasarett, Rheumatol, Falun, Sweden..
    Alenius, Gerd-Marie
    Umea Univ, Publ Hlth & Clin Med Rheumatol, Umea, Sweden..
    Larsson, Per T.
    Karolinska Univ Hosp, Rheumatol, Stockholm, Sweden..
    Teleman, Annika
    Spenshult Hosp, Rheumatol, Olofstrom, Sweden..
    Theander, Elke
    Lund Univ, Skane Univ Hosp, Rheumatol, Malmo, Sweden..
    The Swedish Early Psoriatic Arthritis Registry 5-year Followup: Substantial Radiographic Progression Mainly in Men with High Disease Activity and Development of Dactylitis2015Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, nr 11, s. 2110-2117Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To describe early radiographic findings in patients from the Swedish psoriatic arthritis (SwePsA) registry, progression of destruction, correlations with clinical disease variables, and predictors of destruction. Methods. Hand and foot radiographs were available for 72 of 197 SwePsA patients followed for 5 years. Clinical data were collected according to the SwePsA protocol. Results. Disease characteristics and clinical improvement were similar in men and women. Radiographic abnormalities were more pronounced in men. Total Wassenberg radiographic score at baseline was 0 in 45% of men and 51% of women. One man and one woman had a score >10. At 5 years, total score was 0 in 14% of men and 40% of women (p = 0.018); 17% of men and 7% of women had scores >10. Mean total scores for men and women had increased. Baseline erythrocyte sedimentation rate was associated with baseline total radiographic score. In men, swollen joint count was positively, and in women tender joint count negatively, correlated to total radiographic score. After 5 years, only male scores, mainly hand scores, significantly correlated with 28-joint Disease Activity Score and Disease Activity Index for Psoriatic Arthritis scores, swollen joint count, and dactylitis. Achieving remission or minimal disease activity after 5 years protected against structural damage, mainly in men. Conclusion. Radiographic progression in early PsA was generally slow but substantial. Male sex appears to be a risk factor for early radiographic damage while the presence of baseline radiographic damage and dactylitis developing during followup seem to predict further destruction. Hand and foot radiograph scoring cannot be substituted with clinical signs.

  • 340. Geijer, Mats
    et al.
    Lindqvist, Ulla
    Husmark, Tomas
    Alenius, Gerd-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Larsson, Per T.
    Teleman, Annika
    Theander, Elke
    The Swedish Early Psoriatic Arthritis Registry 5-year Followup: Substantial Radiographic Progression Mainly in Men with High Disease Activity and Development of Dactylitis2015Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, nr 11, s. 2110-2117Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To describe early radiographic findings in patients from the Swedish psoriatic arthritis (SwePsA) registry, progression of destruction, correlations with clinical disease variables, and predictors of destruction.

    Methods: Hand and foot radiographs were available for 72 of 197 SwePsA patients followed for 5 years. Clinical data were collected according to the SwePsA protocol.

    Results: Disease characteristics and clinical improvement were similar in men and women. Radiographic abnormalities were more pronounced in men. Total Wassenberg radiographic score at baseline was 0 in 45% of men and 51% of women. One man and one woman had a score > 10. At 5 years, total score was 0 in 14% of men and 40% of women (p = 0.018); 17% of men and 7% of women had scores > 10. Mean total scores for men and women had increased. Baseline erythrocyte sedimentation rate was associated with baseline total radiographic score. In men, swollen joint count was positively, and in women tender joint count negatively, correlated to total radiographic score. After 5 years, only male scores, mainly hand scores, significantly correlated with 28-joint Disease Activity Score and Disease Activity Index for Psoriatic Arthritis scores, swollen joint count, and dactylitis. Achieving remission or minimal disease activity after 5 years protected against structural damage, mainly in men.

    Conclusion: Radiographic progression in early PsA was generally slow but substantial. Male sex appears to be a risk factor for early radiographic damage while the presence of baseline radiographic damage and dactylitis developing during followup seem to predict further destruction. Hand and foot radiograph scoring cannot be substituted with clinical signs.

  • 341. Gerlag, Danielle M
    et al.
    Raza, Karim
    van Baarsen, Lisa GM
    Brouwer, Elisabeth
    Buckley, Christopher D
    Burmester, Gerd R
    Gabay, Cem
    Catrina, Anca I
    Cope, Andrew P
    Cornelis, Francois
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Emery, Paul
    Eyre, Stephen
    Finckh, Axel
    Gay, Steffen
    Hazes, Johanna M
    van der Helm-van Mil, Annette
    Huizinga, Tom WJ
    Klareskog, Lars
    Kvien, Tore K
    Lewis, Cathryn
    Machold, Klaus P
    Rönnelid, Johan
    van Schaardenburg, Dirkjan
    Schett, Georg
    Smolen, Josef S
    Thomas, Sue
    Worthington, Jane
    Tak, Paul P
    EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis2012Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, nr 5, s. 638-641Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Study Group for Risk Factors for Rheumatoid Arthritis was established by the EULAR Standing Committee on Investigative Rheumatology to facilitate research into the preclinical and earliest clinically apparent phases of rheumatoid arthritis (RA). This report describes the recommendation for terminology to be used to define specific subgroups during different phases of disease, and defines the priorities for research in this area. Terminology was discussed by way of a three-stage structured process: A provisional list of descriptors for each of the possible phases preceding the diagnosis of RA were circulated to members of the study group for review and feedback. Anonymised comments from the members on this list were fed back to participants before a 2-day meeting. 18 participants met to discuss these data, agree terminologies and prioritise important research questions. The study group recommended that, in prospective studies, individuals without RA are described as having: genetic risk factors for RA; environmental risk factors for RA; systemic autoimmunity associated with RA; symptoms without clinical arthritis; unclassified arthritis; which may be used in a combinatorial manner. It was recommended that the prefix 'pre-RA with:' could be used before any/any combination of the five points above but only to describe retrospectively a phase that an individual had progressed through once it was known that they have developed RA. An approach to dating disease onset was recommended. In addition, important areas for research were proposed, including research of other tissues in which an adaptive immune response may be initiated, and the identification of additional risk factors and biomarkers for the development of RA, its progression and the development of extra-articular features. These recommendations provide guidance on approaches to describe phases before the development of RA that will facilitate communication between researchers and comparisons between studies. A number of research questions have been defined, requiring new cohorts to be established and new techniques to be developed to image and collect material from different sites.

  • 342.
    Ghafouri, Bijar
    et al.
    Linkoping Univ, Div Community Med, Dept Med & Hlth Sci, Fac Hlth Sci, SE-58185 Linkoping, Sweden.;Anaesthet Operat & Specialty Surg Ctr, Pain & Rehabil Ctr, SE-58185 Linkoping, Sweden.;Linkoping Univ, Div Neuro & Inflammat Sci, Dept Clin & Expt Med, Occupat & Environm Med Ctr,Heart & Med Ctr, SE-58185 Linkoping, Sweden..
    Carlsson, Anders
    Linkoping Univ, Div Community Med, Dept Med & Hlth Sci, Fac Hlth Sci, SE-58185 Linkoping, Sweden.;Anaesthet Operat & Specialty Surg Ctr, Pain & Rehabil Ctr, SE-58185 Linkoping, Sweden..
    Holmberg, Sara
    Dept Res & Dev, Region Kronoberg, Vaxjo, Sweden..
    Thelin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Tagesson, Christer
    Linkoping Univ, Div Neuro & Inflammat Sci, Dept Clin & Expt Med, Occupat & Environm Med Ctr,Heart & Med Ctr, SE-58185 Linkoping, Sweden..
    Biomarkers of lsystemic inflammation in farmers with musculoskeletal disorders: a plasma proteomic study2016Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, artikel-id 206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Farmers have an increased risk for musculoskeletal disorders (MSD) such as osteoarthritis of the hip, low back pain, and neck and upper limb complaints. The underlying mechanisms are not fully understood. Workrelated exposures and inflammatory responses might be involved. Our objective was to identify plasma proteins that differentiated farmers with MSD from rural referents. Methods: Plasma samples from 13 farmers with MSD and rural referents were included in the investigation. Gel based proteomics was used for protein analysis and proteins that differed significantly between the groups were identified by mass spectrometry. Results: In total, 15 proteins differed significantly between the groups. The levels of leucine-rich alpha-2-glycoprotein, haptoglobin, complement factor B, serotransferrin, one isoform of kininogen, one isoform of alpha-1-antitrypsin, and two isoforms of hemopexin were higher in farmers with MSD than in referents. On the other hand, the levels of alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, vitamin D-binding protein, apolipoprotein A1, antithrombin, one isoform of kininogen, and one isoform of alpha-1-antitrypsin were lower in farmers than in referents. Many of the identified proteins are known to be involved in inflammation. Conclusions: Farmers with MSD had altered plasma levels of protein biomarkers compared to the referents, indicating that farmers with MSD may be subject to a more systemic inflammation. It is possible that the identified differences of proteins may give clues to the biochemical changes occurring during the development and progression of MSD in farmers, and that one or several of these protein biomarkers might eventually be used to identify and prevent work-related MSD.

  • 343.
    Gilljam, Britt-Mari
    et al.
    Högskolan i Halmstad, Akademin för hälsa och välfärd, Centrum för forskning om välfärd, hälsa och idrott (CVHI).
    Arvidsson, Susann
    Högskolan i Halmstad, Akademin för hälsa och välfärd, Centrum för forskning om välfärd, hälsa och idrott (CVHI), Hälsofrämjande processer.
    Nygren, Jens
    Högskolan i Halmstad, Akademin för hälsa och välfärd, Centrum för forskning om välfärd, hälsa och idrott (CVHI), Hälsofrämjande processer.
    Svedberg, Petra
    Högskolan i Halmstad, Akademin för hälsa och välfärd, Centrum för forskning om välfärd, hälsa och idrott (CVHI), Hälsofrämjande processer.
    Promoting participation in healthcare situations for children with JIA: a grounded theory study2016Ingår i: International Journal of Qualitative Studies on Health and Well-being, ISSN 1748-2623, E-ISSN 1748-2631, Vol. 11, artikel-id 30518Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Children’s right to participate in their own healthcare has increasingly become highlighted in national and international research as well as in government regulations. Nevertheless, children’s participation in healthcare is unsatisfactorily applied in praxis. There is a growing body of research regarding children’s participation, but research from the children’s own perspective is scarce. The aim of this study was thus to explore the experiences and preferences for participation in healthcare situations among children with juvenile idiopathic arthritis (JIA) as a foundation for creating strategies to promote their participation in pediatric healthcare. Twenty children, aged 8 to 17 years, with JIA were interviewed individually and in focus groups. In order to increase the children’s opportunities to express their own experiences, different interview techniques were used, such as draw-and-tell and role play with dolls. The analysis was conducted with a constructivist grounded theory. The result explores children’s perspective of influencing processes promoting their participation in healthcare situations. The core category that emerged was, “Releasing fear and uncertainty opens up for confidence and participation,” and the categories related to the core category are, “surrounded by a sense of security and comfort,” and “strengthened and supported to become involved.” In conclusion, the knowledge gained in this study offers new insights from the perspective of children themselves, and can constitute a valuable contribution to the understanding of necessary conditions for the development of specific interventions that promote participation among children in healthcare situations.

  • 344.
    Glerup, Mia
    et al.
    Aarhus Univ Hosp, Dept Pediat, Aarhus N, Denmark.
    Rypdal, Veronika
    UIT Arctic Univ Norway, Dept Clin Med, Tromso, Norway;Univ Hosp North Norway, Dept Pediat, Tromso, Norway.
    Arnstad, Ellen Dalen
    NTNU, Dept Clin & Mol Med, Trondheim, Norway;Levanger Hosp, Dept Pediat, Nord Trondelag, Norway.
    Ekelund, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Ryhov Cty Hosp, Dept Pediat, Jonkoping, Sweden.
    Peltoniemi, Suvi
    Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland.
    Aalto, Kristiina
    Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland.
    Rygg, Marite
    NTNU, Dept Clin & Mol Med, Trondheim, Norway;St Olays Hosp, Dept Pediat, Trondheim, Norway.
    Toftedal, Peter
    Copenhagen Univ Hosp, Dept Pediat, Copenhagen, Denmark.
    Nielsen, Susan
    Copenhagen Univ Hosp, Dept Pediat, Copenhagen, Denmark.
    Fasth, Anders
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Berntson, Lillemor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Nordal, Ellen
    UIT Arctic Univ Norway, Dept Clin Med, Tromso, Norway;Univ Hosp North Norway, Dept Pediat, Tromso, Norway.
    Herlin, Troels
    Aarhus Univ Hosp, Dept Pediat, Aarhus N, Denmark.
    Remission Status after 18 Years of Follow-up in the Population-Based Nordic Juvenile Idiopathic Arthritis (JIA) Cohort2018Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70Artikel i tidskrift (Övrigt vetenskapligt)
  • 345.
    Glerup, Mia
    et al.
    Aarhus Univ Hosp, Dept Pediat, Aarhus N, Denmark.
    Stoustrup, Peter
    Aarhus Univ, Sect Orthodont, Aarhus, Denmark.
    Matzen, Louise Hauge
    Aarhus Univ, Dept Oral Radiol, Aarhus, Denmark.
    Rypdal, Veronika
    Univ Hosp North Norway, Dept Pediat, Tromso, Norway;UIT Arctic Univ Norway, Dept Clin Med, Tromso, Norway.
    Nordal, Ellen
    Univ Hosp North Norway, Dept Pediat, Tromso, Norway;UIT Arctic Univ Norway, Dept Clin Med, Tromso, Norway.
    Frid, Paula
    UIT Arctic Univ Norway, Dept Clin Med, Tromso, Norway;Univ Hosp North Norway, ENT Dept, Div Oral & Maxillofacial Surg, Tromso, Norway;Univ Hosp North Norway, Div Oral & Maxillofacial Surg, Tromso, Norway;Publ Dent Serv Competence Ctr North Norway, Tromso, Norway.
    Arnstad, Ellen Dalen
    NTNU, Dept Clin & Mol Med, Trondheim, Norway;Levanger Hosp, Dept Pediat, Nord Trondelag, Norway.
    Rygg, Marite
    NTNU, Dept Clin & Mol Med, Trondheim, Norway;St Olavs Hosp, Dept Pediat, Trondheim, Norway.
    Thorarensen, Olafur
    NTNU, St Olavs Hosp, Dept Oral & Craniomaxillofacial Surg, Trondheim, Norway.
    Ekelund, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Ryhov Cty Hosp, Dept Pediat, Jonkoping, Sweden.
    Berntson, Lillemor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Fasth, Anders
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Nilsson, Hakan
    Inst Postgrad Dent Educ, Dept Oral & Maxillofacial Surg, Jonkoping, Sweden.
    Peltoniemi, Suvi
    Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland.
    Aalto, Kristiina
    Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland.
    Arte, Sirpa
    Univ Helsinki, Dept Oral & Maxillofacial Dis, Helsinki, Finland.
    Toftedal, Peter
    Copenhagen Univ Hosp, Dept Pediat, Copenhagen, Denmark.
    Nielsen, Susan
    Copenhagen Univ Hosp, Dept Pediat, Copenhagen, Denmark.
    Kreiborg, Sven
    Univ Copenhagen, Dept Paediat Dent & Clin Genet, Copenhagen, Denmark.
    Herlin, Troels
    Aarhus Univ Hosp, Dept Pediat, Aarhus N, Denmark.
    Pedersen, Thomas Klit
    Aarhus Univ, Sect Orthodont, Aarhus, Denmark;Aarhus Univ Hosp, Dept Oral & Maxillofacial Surg, Aarhus, Denmark.
    Long-Term Outcome of Temporomandibular Joint Arthritis in Juvenile Idiopathic Arthritis: Results of 18-Year Follow-up in the Population-Based Nordic JIA Cohort2018Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70Artikel i tidskrift (Övrigt vetenskapligt)
  • 346.
    Glerup, Mia
    et al.
    Aarhus Univ Hosp, Dept Pediat, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark.
    Thiel, Steffen
    Aarhus Univ, Dept Biomed, Aarhus, Denmark.
    Rypdal, Veronika
    Univ Hosp North Norway, Dept Pediat, Tromso, Norway;UiT Arctic Univ Norway, Dept Clin Med, Tromso, Norway.
    Arnstad, Ellen Dalen
    NTNU Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway;Nord Trondelag Hosp Trust, Levanger Hosp, Dept Pediat, Levanger, Norway.
    Ekelund, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammations- och metabolismforskning samt barnhälsa. Ryhov Cty Hosp, Dept Pediat, Jonkoping, Sweden.
    Peltoniemi, Suvi
    Univ Helsinki, Helsinki Univ Cent Hosp, New Childrens Hosp, Pediat Res Ctr, Helsinki, Finland.
    Aalto, Kristiina
    Univ Helsinki, Helsinki Univ Cent Hosp, New Childrens Hosp, Pediat Res Ctr, Helsinki, Finland.
    Rygg, Marite
    NTNU Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway;St Olavs Hosp, Dept Pediat, Trondheim, Norway.
    Nielsen, Susan
    Copenhagen Univ Hosp, Rigshosp, Dept Pediat, Copenhagen, Denmark.
    Fasth, Anders
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden.
    Berntson, Lillemor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammations- och metabolismforskning samt barnhälsa.
    Nordal, Ellen
    Univ Hosp North Norway, Dept Pediat, Tromso, Norway;UiT Arctic Univ Norway, Dept Clin Med, Tromso, Norway.
    Herlin, Troels
    Aarhus Univ Hosp, Dept Pediat, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark.
    Complement lectin pathway protein levels reflect disease activity in juvenile idiopathic arthritis: a longitudinal study of the Nordic JIA cohort2019Ingår i: Pediatric Rheumatology, ISSN 1546-0096, E-ISSN 1546-0096, Vol. 17, nr 1, artikel-id 63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    To determine the serum levels of the lectin pathway proteins early in the disease course and 17 years after disease onset and to correlate the protein levels to markers of disease activity in participants from a population-based Nordic juvenile idiopathic arthritis (JIA) cohort. Additionally, to assess the predictive value of lectin pathway proteins with respect to remission status.

    Methods

    A population-based cohort study of consecutive cases of JIA with a disease onset from 1997 to 2000 from defined geographical areas of Finland, Sweden, Norway and Denmark with 17 years of follow-up was performed. Clinical characteristics were registered and H-ficolin, M-ficolin, MASP-1, MASP-3, MBL and CL-K1 levels in serum were analyzed.

    Results

    In total, 293 patients with JIA were included (mean age 23.7 ± 4.4 years; mean follow-up 17.2 ± 1.7 years). Concentrations of the lectin protein levels in serum were higher at baseline compared to the levels 17 years after disease onset (p ≤ 0.006, n = 164). At baseline, the highest level of M-ficolin was observed in systemic JIA. Further, high M-ficolin levels at baseline and at 17-year follow-up were correlated to high levels of ESR. In contrast, high MASP-1 and MASP-3 tended to correlate to low ESR. CL-K1 showed a negative correlation to JADAS71 at baseline.

    None of the protein levels had prognostic abilities for remission status 17 years after disease onset.

    Conclusion

    We hypothesize that increased serum M-ficolin levels are associated with higher disease activity in JIA and further, the results indicate that MASP-1, MASP-3 and CL-K1 are markers of inflammation.

  • 347. Goldberg, Emily L.
    et al.
    Asher, Jennifer L.
    Molony, Ryan D.
    Shaw, Albert C.
    Zeiss, Caroline J.
    Wang, Chao
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Morozova-Roche, Ludmilla A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Herzog, Raimund I.
    Iwasaki, Akiko
    Dixit, Vishwa Deep
    beta-Hydroxybutyrate deactivates Neutrophil NLRP3 inflammasome to relieve gout flares2017Ingår i: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 18, nr 9, s. 2077-2087Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aging and lipotoxicity are two major risk factors for gout that are linked by the activation of the NLRP3 inflammasome. Neutrophil-mediated production of interleukin-1 beta (IL-1 beta) drives gouty flares that cause joint destruction, intense pain, and fever. However, metabolites that impact neutrophil inflammasome remain unknown. Here, we identified that ketogenic diet (KD) increases beta-hydroxybutyrate (BHB) and alleviates urate crystal-induced gout without impairing immune defense against bacterial infection. BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints. Consistent with reduced gouty flares in rats fed a ketogenic diet, BHB blocked IL-1 beta in neutrophils in a NLRP3-dependent manner in mice and humans irrespective of age. Mechanistically, BHB inhibited the NLRP3 inflammasome in neutrophils by reducing priming and assembly steps. Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as a treatment for gout.

  • 348.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Gaida, Jamie E.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Alfredson, Hakan
    Fowler, Christopher J.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Serum Levels of Oxylipins in Achilles Tendinopathy: An Exploratory Study2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 4, artikel-id e0123114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Linoleic acid-derived oxidation products are found in experimental pain models. However, little is known about the levels of such oxylipins in human pain. In consequence, in the present study, we have undertaken a lipidomic profiling of oxylipins in blood serum from patients with Achilles tendinopathy and controls.

    Methodology/Principal findings: A total of 34 oxylipins were analysed in the serum samples. At a significance level of P<0.00147 (<0.05/34), two linoleic acid-derived oxylipins, 13-hydroxy-10E,12Z-octadecadienoic (13-HODE) and 12(13)-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME) were present at significantly higher levels in the Achilles tendinopathy samples. This difference remained significant when the dataset was controlled for age, gender and body-mass index. In contrast, 0/21 of the arachidonic acid- and 0/4 of the dihomo-γ-linolenic acid, eicosapentaenoic acid or docosahenaenoic acid-derived oxylipins were higher in the patient samples at this level of significance. The area under the Receiver-Operator Characteristic (ROC) curve for 12,13-DiHOME was 0.91 (P<0.0001). Levels of four N-acylethanolamines were also analysed and found not to be significantly different between the controls and the patients at the level of P<0.0125 (<0.05/4).

    Conclusions/Significance: It is concluded from this exploratory study that abnormal levels of linoleic acid-derived oxylipins are seen in blood serum from patients with Achilles tendinopathy. Given the ability of two of these, 9- and 13-HODE to activate transient receptor potential vanilloid 1, it is possible that these changes may contribute to the symptoms seen in Achilles tendinopathy.

  • 349.
    Granqvist, Mathias
    et al.
    Karolinska Inst, Sweden.
    Burman, Joachim
    Uppsala Univ, Sweden.
    Gunnarsson, Martin
    Orebro Univ, Sweden.
    Lycke, Jan
    Sahlgrens Univ Hosp, Sweden.
    Nilsson, Petra
    University Hospital, Lund, Sweden.
    Olsson, Tomas
    Karolinska Inst, Sweden.
    Sundstrom, Peter
    Skane Univ Hosp, Sweden; Umea Univ, Sweden.
    Svenningsson, Anders
    Karolinska Inst, Sweden.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Frisell, Thomas
    Karolinska Inst, Sweden.
    Piehl, Fredrik
    Karolinska Inst, Sweden.
    Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, artikel-id UNSP 1352458519866600Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited. Objective: To evaluate the clinical effectiveness and tolerability of dimethyl fumarate (DMF) as the initial and secondary treatment for relapsing-remitting multiple sclerosis (RRMS) patients compared with common treatment alternatives in Sweden. Methods: We conducted a nationwide retrospective observational cohort study of all RRMS patients identified through the Swedish MS registry initiating DMF (n = 641) or interferons/glatiramer acetate (IFN/GA; n = 555) as the initial therapy, or DMF (n = 703) or fingolimod (FGL; n = 194) after switch from IFN/GA between 1 January 2014 and 31 December 2016. Results: The discontinuation rate was lower with DMF as the initial treatment than IFN/GA (adjusted hazard rate (HR): 0.46, 95% confidence interval (CI): 0.37-0.58, p amp;lt; 0.001), but higher than FGL as the secondary treatment (HR: 1.51, CI: 1.08-2.09, p amp;lt; 0.05). Annualized relapse rate (ARR) was lower with DMF compared to IFN/GA (0.04, CI: 0.03-0.06 vs 0.10, CI: 0.07-0.13; p amp;lt; 0.05), but not FGL (0.03, CI: 0.02-0.05 vs 0.02, CI: 0.01-0.04; p = 0.41). Finally, time to first relapse (TTFR) was longer with DMF as the initial, but not secondary, therapy (p amp;lt; 0.05 and p = 0.20, respectively). Conclusion: Our findings indicate that DMF performs better than IFN/GA as the initial treatment for RRMS. Compared to FGL, DMF displayed a lower tolerability, but largely similar effectiveness outcomes.

  • 350. Gron, K. L.
    et al.
    Ornbjerg, L. M.
    Hetland, M. L.
    Aslam, F.
    Khan, N. A.
    Jacobs, J. W. G.
    Henrohn, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rasker, J. J.
    Kauppi, M. J.
    Lang, H. -C
    Mota, L. M. H.
    Aggarwal, A.
    Yamanaka, H.
    Badsha, H.
    Gossec, L.
    Cutolo, M.
    Ferraccioli, G.
    Gremese, E.
    Lee, E. Bong
    Inanc, N.
    Direskeneli, H.
    Taylor, P.
    Huisman, M.
    Alten, R.
    Pohl, C.
    Oyoo, O.
    Stropuviene, S.
    Drosos, A. A.
    Kerzberg, E.
    Ancuta, C.
    Mofti, A.
    Bergman, M.
    Detert, J.
    Selim, Z. I.
    Abda, E. A.
    Rexhepi, B.
    Sokka, T.
    The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis.: Results from 34 countries participating in the Quest-RA programme2014Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 32, nr 6, s. 869-877Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). Methods Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10 worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score MAW) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. Results Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. Conclusion Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.

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