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  • 301. 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.

  • 302.
    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)
  • 303.
    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.

  • 304.
    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.

  • 305.
    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.

  • 306.
    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.

  • 307. 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.

  • 308. 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.

  • 309.
    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.

  • 310.
    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.

  • 311. 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.

  • 312.
    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.

  • 313. 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.

  • 314.
    Grönwall, Caroline
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Hardt, Uta
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gustafsson, Johanna T.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Elvin, Kerstin
    Karolinska Univ Hosp, Karolinska Inst, Dept Clin Immunol & Transfus Med, Unit Clin Immunol, Stockholm, Sweden..
    Jensen-Urstad, Kerstin
    Karolinska Inst, Dept Clin Physiol, Sodersjukhuset, Stockholm, Sweden..
    Kvarnstrom, Marika
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Grosso, Giorgia
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Padykov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Silverman, Gregg J.
    NYU, Sch Med, Dept Med, Div Rheumatol, New York, NY USA..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Depressed serum IgM levels in SLE are restricted to defined subgroups2017Ingår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 183, s. 304-315Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Strikingly, an autoreactivity profile defined by IgG anti-Ro/La was associated with reduced levels of specific natural IgM targeting phosphoiylcholine (PC) antigens and malondialdehyde (MDA) modified-protein, as well as total IgM, while no differences were detected in SLE patients with an autoreactivity profile defined by anti-cardiolipin/beta(2)glycoprotein-I. We also observed an association of reduced IgM levels with the HEA-DRB1*03 allelic variant among SLE patients and controls. Associations of low IgM anti-PC with cardiovascular disease were primarily found in patients without antiphospholipid antibodies. These studies further highlight the clinical relevance of depressed IgM. Our results suggest that low IgM levels in SLE patients reflect immunological and genetic differences between SLE subgroups.

  • 315.
    Gudbjornsson, B.
    et al.
    Univ Hosp, Ctr Rheumatol Res, Reykjavik, Iceland.
    Laasonen, L.
    Helsinki Med Imaging Ctr, Helsinki, Finland.
    Lindqvist, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Iversen, L.
    Aarhus Univ Hosp, Dept Dermatol, Aarhus, Denmark.
    Ejstrup, L.
    Odense Univ Hosp, Dept Rheumatol, Odense, Denmark.
    Stahle, M.
    Karolinska Inst, Dermatol Unit, Stockholm, Sweden.
    Radiographic features of psoriatic arthritis mutilans: results from the Nordic PAM Study2018Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, s. 60-61Artikel i tidskrift (Övrigt vetenskapligt)
  • 316.
    Gudbjörnsson, B.
    et al.
    Univ Hosp, Ctr Rheumatol Res, Reykjavik, Iceland..
    Lindqvist, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Iversen, L.
    Aarhus Univ Hosp, Aarhus, Denmark..
    Paimela, L.
    Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland..
    Laasonen, L.
    Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland..
    Ejstrup, L.
    Odense Univ Hosp, Odense, Denmark..
    Ternowitz, T.
    Stavanger Univ Hosp, Stavanger, Norway..
    Stahle, M.
    Karolinska Inst, Dept Med, S-10401 Stockholm, Sweden..
    Disease activity and quality of life of patients with psoriatic arthritis mutilans: the Nordic PAM study2016Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 45, s. 33-33Artikel i tidskrift (Övrigt vetenskapligt)
  • 317.
    Gunasekera, Sunithi
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Fernandes-Cerqueira, Catia
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Rheumatol Clin D2 01, S-17176 Stockholm, Sweden.
    Wennmalm, Stefan
    Royal Inst Technol KTH, Scilifelab, Appl Phys, Expt Biomol Phys, Tomtebodavagen 23, S-17165 Stockholm, Sweden.
    Wahamaa, Heidi
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Rheumatol Clin D2 01, S-17176 Stockholm, Sweden.
    Sommarin, Yngve
    Eurodiagnost AB, S-21224 Malmo, Sweden.
    Catrina, Anca, I
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Rheumatol Clin D2 01, S-17176 Stockholm, Sweden.
    Jakobsson, Per-Johan
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Rheumatol Clin D2 01, S-17176 Stockholm, Sweden.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Stabilized Cyclic Peptides as Scavengers of Autoantibodies: Neutralization of Anticitrullinated Protein/Peptide Antibodies in Rheumatoid Arthritis2018Ingår i: ACS Chemical Biology, ISSN 1554-8929, E-ISSN 1554-8937, Vol. 13, nr 6, s. 1525-1535Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The occurrence of autoantibodies is a hallmark of rheumatoid arthritis, specifically those autoantibodies targeting proteins containing the arginine-derived amino acid citrulline. There is strong evidence showing that the occurrence of anticitrullinated protein/peptide antibodies (ACPA) are involved in disease progression, and ACPA was recently shown to induce pain in animals. Here, we explore a novel concept useful for research, diagnostics, and possibly therapy of autoimmune diseases, namely, to directly target and neutralize autoantibodies using peptide binders. A high-affinity peptide-based scavenger of ACPA was developed by grafting a citrullinated epitope derived from human fibrinogen into a naturally occurring stable peptide scaffold. The best scavenger comprises the truncated epitope alpha-fibrinogen, [Cit573]fib(566-580), grafted into the scaffold sunflower trypsin inhibitor-1, SFTI-1. The final peptide demonstrates low nanomolar apparent affinity and superior stability.

  • 318.
    Guo, Xiong
    et al.
    Institute of Endemic Diseases, Medical College of Xi'an Jiaotong University, Xi'an, China.
    Lammi, Mikko
    Institute of Molecular Medicine, University of Erlangen-Nurnberg, Erlangen, Germany.
    Aigner, Thomas
    Department of Pathology, University of Erlangen-Nurnberg, Erlangen, Germany.
    Lammi, Pirkko
    Institute of Molecular Medicine, University of Erlangen-Nurnberg, Erlangen, Germany.
    Vornehm, Silvia
    Institute of Molecular Medicine, University of Erlangen-Nurnberg, Erlangen, Germany.
    Yu, Zhidao
    Institute of Endemic Diseases, Medical College of Xi'an Jiaotong University, Xi'an, China.
    Xiong, Yongmin
    Institute of Endemic Diseases, Medical College of Xi'an Jiaotong University, Xi'an, China.
    von der Mark, Klaus
    Institute of Molecular Medicine, University of Erlangen-Nurnberg, Erlangen, Germany.
    Effect of low selenium on chondrocyte differentation and differential expression of collagen types I, II and X in articular cartilage from mini-pigs2000Ingår i: Journal of Xi'an Medical University, ISSN 1671-8259, Vol. 12, s. 108-112Artikel i tidskrift (Övrigt vetenskapligt)
  • 319.
    Guo, Xiong
    et al.
    Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University, Xi'an, China.
    Ma, Wei-Juan
    Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University, Xi'an, China.
    Zhang, Feng
    Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University, Xi'an, China.
    Ren, Feng-Lin
    Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University, Xi'an, China.
    Qu, Cheng-Juan
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Recent advances in the research of an endemic osteochondropathy in China: Kashin-Beck disease2014Ingår i: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 22, nr 11, s. 1774-1783, artikel-id 25106677Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Kashin-Beck disease (KBD) is an endemic chronic osteochondral disease, which has a high prevalence and morbidity in the Eastern Siberia of Russia, and in the broad diagonal, northern-east to southern-west belt in China and North Korea. In 1990's, it was estimated that in China 1–3 million people had some degree of symptoms of the disease, although even higher estimates have been presented. In China, the extensive prevalence peaked in the late 1950's, but since then, in contrast to the global trend of the osteoarthritis (OA), the number of cases has been dramatically falling. Up to 2013, there are 0.64 millions patients with the KBD and 1.16 millions at risk in 377 counties of 13 provinces or autonomous regions. This is obviously thanks to the preventive efforts carried out, which include providing millions of people with dietary supplements and clean water, as well as relocation of whole villages in China. However, relatively little is known about the molecular mechanisms behind the cartilage damage, the genetic and the environmental risk factors, and the rationale of the preventive effects. During the last decade, new data on a cellular and molecular level has begun to accumulate, which hopefully will uncover the grounds of the disease.

  • 320. Gustafsson, J.
    et al.
    Jensen-Urstad, K.
    Herlitz-Lindberg, M.
    Moller, S.
    Pettersson, S.
    Gunnarsson, I.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Svenungsson, E.
    Atherosclerosis in systemic lupus erythematosus (SLE) and controls: an analysis of SLE subgroups2014Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr S127, s. 7-8Artikel i tidskrift (Övrigt vetenskapligt)
  • 321. Gustafsson, Johanna
    et al.
    Simard, Julia F
    Gunnarsson, Iva
    Elvin, Kerstin
    Lundberg, Ingrid E
    Hansson, Lars-Olof
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Svenungsson, Elisabet
    Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study2012Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 14, nr 2, s. R46-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION:

    Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate causes of death and baseline predictors of overall (OM), non-vascular (N-VM), and specifically cardiovascular (CVM) mortality in SLE, and to evaluate Systematic coronary risk evaluation (SCORE).

    METHODS:

    208 SLE patients were included 1995-1999 and followed up after 12 years. Clinical evaluation, CVD risk factors, and biomarkers were recorded at inclusion. Death certificates and autopsy protocols were collected. Causes of death were divided into CVM (ischemic vascular and general atherosclerotic diseases), N-VM and death due to pulmonary hypertension. Predictors of mortality were investigated using multivariable Cox regression. SCORE and standardized mortality ratio (SMR) were calculated.

    RESULTS:

    During follow-up 42 patients died at mean age of 62 years. SMR 2.4 (CI 1.7-3.0). 48% of deaths were caused by CVM. SCORE underestimated CVM but not to a significant level. Age, high cystatin C levels and established arterial disease were the strongest predictors for all- cause mortality. After adjusting for these in multivariable analyses, only smoking of traditional risk factors, high soluble vascular cell adhesion molecule-1 (sVCAM-1), high sensitivity C-reactive protein (hsCRP), anti-beta2 glycoprotein-1 (abeta2GP1) and any antiphospholipid antibody (aPL) among biomarkers, remained predictive of CVM.

    CONCLUSION:

    With the exception of smoking, traditional risk factors do not capture the main underlying risk factors for CVM in SLE. Rather, cystatin C levels, inflammatory and endothelial markers, and anticardiolipin antibodies (aCL) differentiate patients with favorable versus severe cardiovascular prognosis. Our results suggest that these new biomarkers are useful in evaluating the future risk of cardiovascular mortality in SLE patients.

  • 322. Gustafsson, Johanna T
    et al.
    Herlitz Lindberg, Marie
    Gunnarsson, Iva
    Pettersson, Susanne
    Elvin, Kerstin
    Öhrvik, John
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Jensen-Urstad, Kerstin
    Svenungsson, Elisabet
    Excess atherosclerosis in systemic lupus erythematosus A matter of renal involvement: Case control study of 281 SLE patients and 281 individually matched population controls2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 4, artikel-id e0174572Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups.

    METHODS: 281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls.

    RESULTS: Median age was 49 (IQR 36-59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035).

    CONCLUSIONS: In SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. In a general perspective this study demonstrates the importance to perform careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE.

  • 323. Hafstrom, Ingiald
    et al.
    Engvall, Inga-Lill
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Boonen, Annelies
    van der Heijde, Desiree
    Svensson, Bjorn
    Rheumatoid factor and anti-CCP do not predict progressive joint damage in patients with early rheumatoid arthritis treated with prednisolone: a randomised study2014Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 4, nr 7, s. e005246-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To analyse if predictors of radiographic progression differ between patients treated with or without prednisolone in early rheumatoid arthritis (RA). Radiographs of hands and feet were assessed using the modified Sharp/van der Heijde score and radiographic progression was defined as an increase in the total Sharp score above 5.8 (the smallest detectable change). Design: Prospective, randomised study of patients with early RA. Setting: Secondary level of care; six participating centres from southern Sweden; both urban and rural populations. Participants: In all, 225 patients, 64% women, with a diagnosis of RA according to the American College of Rheumatology criteria, were included if they were between 18 and 80 years of age and had a disease duration of less than 1 year. Intervention: The patients were randomised to 7.5 mg prednisolone daily for 2 years (P-group; n=108) or no prednisolone (NoP-group; n=117) when they started with their first disease-modifying anti-rheumatic drug and were prospectively followed for 2 years. Results: The frequency of patients with radiographic progression after 2 years was 26% in the P-group and 39% in the NoP-group (p=0.033). Relevant interactions between treatment and rheumatoid factor (RF) (p=0.061) and between treatment and anti-cyclic citrullinated peptide 2 (anti-CCP) (p=0.096) were found. RF and anti-CCP independently predicted radiographic progression only in the NoP-group, OR (95% CI) 9.4 (2.5 to 35.2), p=0.001 and OR (95% CI) 8.7 (2.5 to 31.3), p=0.001, respectively. Conclusions: The presence of RF and anti-CCP predicted radiographic progression in patients not treated with prednisolone but failed to predict progression in patients treated with this drug. The data suggest that early treatment with prednisolone may modulate not only inflammation but also autoimmunity-associated pathogenetic mechanisms.

  • 324.
    Hagberg, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    The Role of Plasmacytoid Dendritic Cells and Natural Killer Cells in Systemic Lupus Erythematosus2014Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production, which can eventually lead to immune complex (IC)-mediated organ damage. Due to the stimulation of plasmacytoid dendritic cells (pDC) by nucleic acid-containing ICs (DNA- or RNA-IC), patients with SLE have an ongoing interferon (IFN)-α production. IFN-α induces a general activation of the immune system that may initiate or propagate an autoimmune process if not properly regulated. Previous studies have shown that natural killer (NK) cells potently enhance the IFN-α production by pDCs.

    In study I, the mechanisms behind the NK cell-mediated increased IFN-α production by RNA-IC-stimulated pDCs were investigated. ICs triggered CD56dim NK cells via FcγRIIIA to the secretion of cytokines (e.g. MIP-1β) that promoted IFN-α production. Additionally, an LFA-1-dependent cell-cell interaction between pDCs and NK cells strongly contributed to the increased production of IFN-α. In study II, the RNA-IC-induced regulation of surface molecules on pDCs and NK cells was investigated. The expression of CD319 and CD229, which are two SLAM family receptors genetically associated with SLE, was induced on pDCs and NK cells by RNA-IC. IFN-α-producing pDCs displayed an increased expression of CD319 and CD229, whereas pDCs from patients with SLE had a decreased expression of CD319. In study III, we serendipitously identified an SLE patient harboring autoantibodies to the NK cell receptor CD94/NKG2A. In study IV, sera from 203 patients with SLE were analyzed for autoantibodies to the CD94/NKG2A, CD94/NKG2C and NKG2D receptors. Seven patients harbored anti-CD94/NKG2A autoantibodies, and two of these patient’s autoantibodies also reacted with CD94/NKG2C. Anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies both interfered with the HLA-E-mediated regulation of NK cell cytotoxicity, and facilitated the elimination of target cells expressing these receptors. Furthermore, these autoantibodies were found in a group of severely diseased SLE patients and their titers closely followed disease activity.

    In conclusion, this thesis provides insights to molecular mechanisms whereby NK cells regulate the IFN-α production, it further links the SLAM receptors to SLE, and it describes novel autoantibodies to receptors regulating NK cell cytotoxicity. Together these findings strengthen the assumption that NK cells are involved in the pathogenesis of SLE.

  • 325.
    Hagberg, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Berggren, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Weber, Gert
    Bryceson, Yenan T.
    Alm, Gunnar V.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    IFN-α Production by Plasmacytoid Dendritic Cells Stimulated with RNA-Containing Immune Complexes Is Promoted by NK Cells via MIP-1β and LFA-12011Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 186, nr 9, s. 5085-5094Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several systemic autoimmune diseases display a prominent IFN signature. This is caused by a continuous IFN-α production by plasmacytoid dendritic cells (pDCs), which are activated by immune complexes (ICs) containing nucleic acid. The IFN-α production by pDCs stimulated with RNA-containing IC (RNA-IC) consisting of anti-RNP autoantibodies and U1 small nuclear ribonucleoprotein particles was recently shown to be inhibited by monocytes, but enhanced by NK cells. The inhibitory effect of monocytes was mediated by TNF-α, PGE2, and reactive oxygen species, but the mechanisms for the NK cell-mediated increase in IFN-α production remained unclear. In this study, we investigated the mechanisms whereby NK cells increase the RNA-IC–induced IFN-α production by pDCs. Furthermore, NK cells from patients with systemic lupus erythematosus (SLE) were evaluated for their capacity to promote IFN-α production. We found that CD56dim NK cells could increase IFN-α production >1000-fold after RNA-IC activation, whereas CD56bright NK cells required costimulation by IL-12 and IL-18 to promote IFN-α production. NK cells produced MIP-1α, MIP-1β, RANTES, IFN-γ, and TNF-α via RNA-IC–mediated FcγRIIIA activation. The IFN-α production in pDCs was promoted by NK cells via MIP-1β secretion and LFA-mediated cell–cell contact. Moreover, NK cells from SLE patients displayed a reduced capacity to promote the RNA-IC–induced IFN-α production, which could be restored by exogenous IL-12 and IL-18. Thus, different molecular mechanisms can mediate the NK cell-dependent increase in IFN-α production by RNA-IC–stimulated pDCs, and our study suggests that the possibility to therapeutically target the NK–pDC axis in IFN-α–driven autoimmune diseases such as SLE should be investigated.

  • 326.
    Hagberg, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Joelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Reid, Sarah
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Mo, John
    Nilsson, Magnus K
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Bryceson, Yenan T
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE.2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, artikel-id annrheumdis-2017-212794Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: risk allele rs7574865[T] affects the function of immune cells in SLE.

    METHODS: risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs.

    RESULTS: risk patients, respectively.

    CONCLUSIONS: risk allele rs7574865[T] display an augmented response to IL-12 and IFN-α. This subset of patients may benefit from JAKi treatment.

  • 327.
    Hagberg, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Systemic lupus erythematosus: a disease with a dysregulated type I interferon system2015Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 82, nr 3, s. 199-207Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the loss of tolerance to nuclear antigens, immune complex formation and inflammation in multiple organs. The disease is very heterogeneous and most clinicians consider SLE as a group of diseases with similar features where the pathogenesis is driven by a combination of genetic and environmental factors. One of the most prominent features, shared by the majority of SLE patients, is a continuous activation of the type I interferon (IFN) system, which manifests as increased serum levels of IFNα and/or an increased expression of type I IFN induced genes, a so called type I IFN-signature. The mechanisms behind this IFN-signature have partly been clarified during recent years, although the exact function of the IFN regulated genes in the disease process is unclear. In this review we will describe the type I IFN system and its regulation and summarize the numerous findings implicating an important ethiopathogenic role of a dysregulated type I IFN system in SLE. Furthermore, strategies to therapeutically target the type I IFN system that are currently evaluated preclinically and in clinical trials will be mentioned.

  • 328.
    Hagberg, Niklas
    et al.
    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.
    The Interferon System in Lupus Erythematosus2016Ingår i: Systemic Lupus Erythematosus: Basic, Applied and Clinical Aspects / [ed] George C. Tsokos, Academic Press, 2016, s. 153-158Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    The interferons (IFNs) are a large group of proteins classified into three types (I-III) that induce viral resistance in cells and also act as immune adjuvants and stimulate the adaptive immune system. Increased levels of mainly type I IFN are seen in patients with systemic lupus erythematosus (SLE), which is due to the presence of self-derived inducers of type I IFN production acting on plasmacytoid dendritic cells. Such inducers consist of autoantigens containing nucleic acid that stimulate endosomal Toll-like receptors, which trigger the ongoing IFN synthesis that leads to an increased transcription of type I IFN-regulated genes in target cells (an interferon signature). The type I IFN production contributes to the autoimmune process and several therapies aiming to inhibit the production, or action, of type I IFN have been developed. Preliminary results indicate that this therapeutic strategy may be successful in a subset of patients with SLE.

  • 329.
    Hagberg, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Theorell, Jakob
    Alm, Gunnar V.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Bryceson, Yenan
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    SLE immune complexes upregulate the expression of slamf7 (cd319) on plasmacytoid dendritic cells2012Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, s. A3-A3Artikel i tidskrift (Övrigt vetenskapligt)
  • 330.
    Hagberg, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Theorell, Jakob
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Pascal, Veronique
    Bryceson, Yenan T
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Anti-NKG2A autoantibodies in a patient with systemic lupus erythematosus2013Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 52, nr 10, s. 1818-1823Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives

    To characterize a novel anti-NKG2A autoantibody detected in a patient with SLE during a severe flare, and in a cross-sectional study investigate the occurrence of such autoantibodies in patients with SLE and primary SS (pSS).

    Methods

    Serum or IgG from patients with SLE, pSS and healthy volunteers were assayed for blocking of anti-NKG2A or HLA-E binding to peripheral blood mononuclear cells or CD94/NKG2A- and CD94/NKG2C-transfected Ba/F3 cells. The anti-NKG2A autoantibodies were evaluated for effect on NK cell degranulation in response to HLA-E-transfected K562 cells. IFN-α was determined by an immunoassay and disease activity by the SLEDAI score.

    Results

    Anti-NKG2A autoantibodies, which blocked binding of HLA-E tetramers to CD94/NKG2A-transfected cells and impaired NKG2A-mediated inhibition of NK cell activation, were observed in a patient with SLE. The presence of anti-NKG2A autoantibodies was associated with high SLE disease activity (SLEDAI score 14 and 16) and increased serum IFN-α. Of 94 SLE, 60 pSS and 30 healthy donor sera, only the index patient serum contained anti-NKG2A autoantibodies.

    Conclusion

    The presence of autoantibodies targeting NKG2A is a rare event, but when such autoantibodies occur they may promote excessive NK cell function. This can contribute to the pathogenesis by increasing the killing of cells and the release of autoantigens. Our findings highlight the possible importance of NK cells in the SLE disease process.

  • 331.
    Hagberg, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Theorell, Jakob
    Hjorton, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Spee, Pieter
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Bryceson, Yenan T.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Functional Anti-CD94/NKG2A and Anti-CD94/NKG2C Autoantibodies in Patients With Systemic Lupus Erythematosus2015Ingår i: ARTHRITIS & RHEUMATOLOGY, ISSN 2326-5191, Vol. 67, nr 4, s. 1000-1011Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Recently we serendipitously identified a patient with systemic lupus erythematosus (SLE) who was positive for autoantibodies to CD94/natural killer receptor group 2A (NKG2A). The present study was undertaken to investigate the occurrence and function of autoantibodies targeting lectin-like NK cell receptors in SLE. Methods. Sera from 203 SLE patients and 90 healthy individuals were analyzed, by flow cytometry, for Ig binding to Ba/F3 cells transfected with CD94/NKG2A, CD94/NKG2C, or NKG2D. Autoantibodies identified were characterized with regard to interference with HLA-E binding, effect on NK cell activation in response to HLA-E-transfected K562 cells, and capacity to facilitate antibody-dependent cell-mediated cytotoxicity (ADCC). Levels of autoantibodies were determined in longitudinally sampled sera, and correlations with disease activity (SLE Disease Activity Index 2000) and severity (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were investigated. Results. Anti-CD94/NKG2A autoantibodies were identified in 7 SLE patients. The autoantibodies from 6 patients inhibited binding of HLA-E to CD94/NKG2A, whereas those from the seventh patient augmented this binding. Autoantibodies from 2 patients also reacted with the activating receptor CD94/NKG2C, with inhibition of the binding of HLA-E to CD94/NKG2C observed in 1 case and enhancement of this binding in the other. None of the sera contained anti-NKG2D autoantibodies. The levels of anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies correlated with disease activity and with a more severe SLE phenotype. Mechanistically, anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies both interfered with HLA-E-mediated regulation of NK cell activation and facilitated the elimination of target cells expressing CD94/NKG2A or CD94/NKG2C through ADCC. Conclusion. Anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies occur in a subset of patients with clinically active SLE. Given their capacity to deplete certain NK cell subsets and interfere with particular NK cell function, such autoantibodies may promote the pathogenesis of SLE.

  • 332.
    Hagel, Sofia
    et al.
    Department of Clinical Sciences Lund, Section of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
    Petersson, Ingemar F
    Department of Orthopedics, Lund University, Lund, Sweden.
    Bremander, Ann
    Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, Bio- och miljösystemforskning (BLESS), Biomekanik och biomedicin.
    Lindqvist, Elisabet
    Department of Clinical Sciences Lund, Section of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
    Bergknut, Charlotte
    Department of Orthopedics, Lund University, Lund, Sweden.
    Englund, Martin
    Department of Orthopedics, Lund University, Lund, Sweden.
    Trends in the first decade of 21st century healthcare utilisation in a rheumatoid arthritis cohort compared with the general population2012Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, nr 7, s. 1212-1216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To study 21st century trends in healthcare utilisation by patients with rheumatoid arthritis (RA) compared with the general population.

    Methods: Observational cohort study. Using Swedish healthcare register data, we identified 3977 Region Skåne residents (mean age in 2001, 62.7 years; 73% women) presenting with RA (International Classification of Diseases-10 codes M05 or M06) in 1998-2001. We randomly sampled two referents from the general population per RA patient matched for age, sex and area of residence. We calculated the year 2001-2010 trends for the annual ratio (RA cohort/referents) of the mean number of hospitalisations and outpatient clinic visits.

    Results: By the end of the 10-year period, 62% of patients and 74% of referents were still alive and resident in the region. From 2001 to 2010, the ratio (RA cohort/referents) of the mean number of hospitalisations for men and women decreased by 27% (p=0.01) and 28% (p=0.004), respectively. The corresponding decrease was 29% (p=0.005) and 16% (p=0.004) for outpatient physician care, 34% (p=0.009) and 18% (p=0.01) for nurse visits, and 34% (p=0.01) and 28% (p=0.004) for physiotherapy. The absolute reduction in number of hospitalisations was from an annual mean of 0.79 to 0.69 in male patients and from 0.71 to 0.59 in female patients. The corresponding annual mean number of consultations in outpatient physician care by male and female RA patients changed from 9.2 to 7.7 and from 9.9 to 8.7, respectively.

    Conclusions: During the first decade of the 21st century, coinciding with increasing use of earlier and more active RA treatment including biological treatment, overall inpatient and outpatient healthcare utilisation by a cohort of patients with RA decreased relative to the general population. Copyright Article author (or their employer) 2012.

  • 333. Hagelberg, Stefan
    et al.
    Andersson Gäre, BoelHögskolan i Jönköping, Hälsohögskolan, The Jönköping Academy for Improvement of Health and Welfare.Fasth, AndersMånsson, BengtEnman, Yvonne
    Barnreumatologi2008Samlingsverk (redaktörskap) (Övrigt vetenskapligt)
  • 334.
    Hager, Charlotte
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Changes in sensorimotor behaviour with pain and how to capture these in a movement analysis laboratory2012Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 51, s. 14-15Artikel i tidskrift (Övrigt vetenskapligt)
  • 335. Haldorsen, K
    et al.
    Appel, S
    Le Hellard, S
    Bruland, O
    Brun, J G
    Omdal, R
    Kristjansdottir, Gudlaug
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Theander, E
    Fernandes, C P D
    Kvarnström, M
    Eriksson, P
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Herlenius, M W
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Jonsson, R
    Bolstad, A I
    No association of primary Sjogren's syndrome with Fc gamma receptor gene variants2013Ingår i: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 14, nr 4, s. 234-237Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The genetic background of primary Sjögren's syndrome (pSS) is partly shared with systemic lupus erythematosus (SLE). Immunoglobulin G Fc receptors are important for clearance of immune complexes. Fcγ receptor variants and gene deletion have been found to confer SLE risk. In this study, four Fcγ receptor single-nucleotide polymorphisms (SNPs) and one copy number variation (CNV) were studied. Swedish and Norwegian pSS patients (N=527) and controls (N=528) were genotyped for the Fcγ receptor gene variant FCGR2A H131R (rs1801274) by the Illumina GoldenGate assay. FCGR3A F158V (rs396991) was analysed in 488 patients and 485 controls, FCGR3B rs447536 was analysed in 471 patients and 467 controls, and FCGR3B rs448740 was analysed in 478 cases and 455 controls, using TaqMan SNP genotyping assays. FCGR3B CNV was analysed in 124 patients and 139 controls using a TaqMan copy number assay. None of the SNPs showed any association with pSS. Also, no FCGR3B CNV association was detected. The lack of association of pSS with Fcγ receptor gene variants indicates that defective immune complex clearance may not be as important in pSS pathogenesis as in SLE, and may point to important differences between SLE and pSS.

  • 336.
    Hallert, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Disease activity, function and costs in early rheumatoid arthritis2006Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Rheumatoid arthritis (RA) is a major cause of progressive joint damage and disability, and is associated with decline in quality of life, reduced ability to work and increased health care utilisation. The economic consequences of the disease are substantial for the individuals and their families and for the society as a whole. This thesis describes a 5-year follow up of 320 patients with early RA, enrolled between January 1996 and April 1998 in the Swedish multi-centre inception cohort TIRA (early interventions in rheumatoid arthritis). Health status, function and costs were investigated. Predictors of high costs were calculated, and an algorithm was constructed to predict future need for TNFinhibitor treatment in patients not responding to traditional disease-modifying antirheumatic drugs (DMARDs). Clinical and laboratory data, measures of functional capacity and self-reported assessments were collected regularly. In addition, patients completed biannual/annual questionnaires concerning all health care utilisation and days lost from work due to the disease. Within 3 months, improvements were seen regarding all variables assessing disease activity and functional ability, but 15% of the patients had sustained high or moderate disease activity throughout the study period. The scores of ‘health assessment questionnaire’ (HAQ) were similar for men and women at baseline, but had a less favourable course in women, who also had DMARDs more frequently prescribed.

    Ambulatory care accounted for 76% of the direct costs during the first year. Women had more ambulatory care visits and higher usage of complementary medicine compared to men. Men ≥65 years had low costs compared to younger men and compared to women of all ages. In multiple logistic regression tests, HAQ, high levels of IgM-class rheumatoid factor (RF), and poor hand function increased the odds of incurring high direct costs. Poor hand function and pain increased the odds of incurring high indirect costs.

    Indirect costs exceeded direct costs all three years. The average direct costs were €3,704 (US$ 3,297) year 1 and €2,652 (US$ 2,360) year 3. All costs decreased over the years, except those for medication and surgery. The indirect costs were €8,871 (US$ 7,895) year 1 and remained essentially unchanged, similarly for both sexes. More than 50% were on sick leave or early retirement at inclusion. Sick leave decreased but was offset by increase in early retirement. 14 patients (5%) were prescribed TNF-inhibitors at the 3- year follow up, thus increasing drug costs substantially. However, they incurred higher costs even before prescription of anti-TNF therapy.

    At the 5-year follow-up (2001-2003), 31 patients (12%) were prescribed TNFinhibitors. Baseline values of erythrocyte sedimentation rate, C-reactive protein, anti-CCP antibodies and morning stiffness were significantly higher in this group. These patients were also to a larger extent RF-positive and carriers of the ‘shared epitope’ (SE). Anti-TNF treated patients were significantly younger and more often women. For men, a predictive model was constructed using baseline data including SE+ and IgA-RF >100 U/L and anti-CCP >240 U/L yielding a specificity of 98% and a sensitivity of 71%. For women, disease activity score (DAS28) at the 3-month follow-up proved to be a better predictor, and the final model comprised SE+ and 3-month DAS28>5.2, giving a specificity of 95% and a sensitivity of 59%.

  • 337.
    Hallert, Eva
    et al.
    Linköping University.
    Björk, Mathilda
    Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för rehabilitering. Högskolan i Jönköping, Hälsohögskolan, HHJ. ADULT.
    Dahlström, Örjan
    Linköping University.
    Skogh, Thomas
    Linköping University.
    Thyberg, Ingrid
    Linköping University.
    Disease activity and disability in women and men with early rheumatoid arthritis (RA): An 8-year followup of a Swedish early RA project2012Ingår i: Arthritis Care and Research, ISSN 0893-7524, E-ISSN 1529-0123, Vol. 64, nr 8, s. 1101-1107Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To compare women and men regarding course of disease activity and disability over 8 years from diagnosis of recent onset rheumatoid arthritis (RA).

    PATIENTS AND METHODS: 149 patients were followed for 8 years from RA diagnosis (1996-98) regarding 28-joint count disease activity score (DAS28), pain (visual analogue scale, VAS), grip force, Grip Ability Test (GAT), Signals of Functional Impairment (SOFI hand, upper/lower extremity), walking speed, activity limitation (Health Assessment Questionnaire, HAQ) and prescribed disease-modifying anti-rheumatic drugs (DMARDs).

    RESULTS: Disease activity pattern over time was similar in women and men, showing improvement during the first year and thereafter a stable situation during 6 years. However, at the 7- and 8-year follow-ups deterioration was seen with a less favourable course in women. HAQ did not differ between sexes at diagnosis, but at all follow-ups women had significantly higher scores than men. Women also had lower grip force and lower walking speed, but higher upper extremity mobility. DMARD prescription was similar for both sexes. Over eight years, disease duration, sex, biologics, grip force, SOFI-hand and pain intensity together explained 43% of the variation in DAS, while grip force, SOFI-lower, GAT and pain intensity could together explain 55% of variations in HAQ.

    CONCLUSIONS: Disease activity was fairly well managed, but disability gradually deteriorated. Despite similar medication, women had more disability than men. The discrepancy between disease activity and disability indicates unmet needs for multi-professional interventions to prevent progressing disability and patients at risk for disability need to be identified early in the process. © 2012 by the American College of Rheumatology.

  • 338.
    Hallert, Eva
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Utvärdering och hälsoekonomi. Linköpings universitet, Hälsouniversitetet.
    Björk, Mathilda
    Avd. för rehabilitering, HHJ, Hälsohögskolan, Högskolan i Jönköping.
    Thyberg, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet.
    Development of disease activity and disability in women and men with early rheumatoid arthritis: 8 years of follow-up from the Swedish TIRA-project2010Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Background: Previous studies have reported that disability is strongly associated with disease activity in rheumatoid arthritis (RA) and disability at time of diagnosis has also proved to be a consistent predictor of disability over time.Objectives: To investigate the course of disease activity and disability over 8 years in early RA and to analyse differences between women and men.Methods: 149 patients with disease duration <1 year were included in the Swedish early RA-cohort "TIRA". Patients were followed prospectively for 8 years from the time of diagnosis. Disease activity was assessed by DAS28. Disability was measured by pain (VAS), grip force (Grippit), 'grip ability test' (GAT), range of motion in hand, upper and lower extremity (SOFI), walking speed and Health Assessment Questionnaire (HAQ). Changes over time and differences between women and men were evaluated.Results: Disease activity decreased over time from inclusion to the 8-year follow-up for both women and men. Disability as measured by SOFI (hand, upper and lower extremity) and walking time was improved during the first year after diagnosis but at the 7 and 8 year follow-up, the level of disability was comparable to the level at inclusion. Pain, grip force and GAT were also improved during the first years but thereafter remained stable. HAQ scores were similar in men and women at inclusion. After initial improvement, HAQ remained at a stable level in men, while scores for women deteriorated from year 2 onwards and had reached back to baseline levels at 8 year follow-up. More disability in women than men was also seen in grip force whereas men had more disability than women in SOFI upper extremity. There were no significant differences between women and men in disease activity or disability as measured by VAS pain, GAT, SOFI hand or SOFI lower extremity during the 8-year follow-up.Conclusion: Although disease activity was well managed, disability deteriorated over 8 years with a less favourable course in women than men. Besides controlling disease activity, there is accordingly a need for regular assessments to detect and prevent progressing disability in RA-patients, not only in the early phase of disease, but also over the following years

  • 339.
    Hallert, Eva
    et al.
    Linköping University.
    Björk, Mathilda
    Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för rehabilitering.
    Thyberg, Ingrid
    Linköping University.
    Development of disease activity and disability in women and men with early rheumatoid arthritis: 8 years of follow-up from the Swedish TIRA-project2010Konferensbidrag (Refereegranskat)
    Abstract [en]

    Background: Previous studies have reported that disability is strongly associated with disease activity in rheumatoid arthritis (RA) and disability at time of diagnosis has also proved to be a consistent predictor of disability over time.Objectives: To investigate the course of disease activity and disability over 8 years in early RA and to analyse differences between women and men.Methods: 149 patients with disease duration <1 year were included in the Swedish early RA-cohort "TIRA". Patients were followed prospectively for 8 years from the time of diagnosis. Disease activity was assessed by DAS28. Disability was measured by pain (VAS), grip force (Grippit), 'grip ability test' (GAT), range of motion in hand, upper and lower extremity (SOFI), walking speed and Health Assessment Questionnaire (HAQ). Changes over time and differences between women and men were evaluated.Results: Disease activity decreased over time from inclusion to the 8-year follow-up for both women and men. Disability as measured by SOFI (hand, upper and lower extremity) and walking time was improved during the first year after diagnosis but at the 7 and 8 year follow-up, the level of disability was comparable to the level at inclusion. Pain, grip force and GAT were also improved during the first years but thereafter remained stable. HAQ scores were similar in men and women at inclusion. After initial improvement, HAQ remained at a stable level in men, while scores for women deteriorated from year 2 onwards and had reached back to baseline levels at 8 year follow-up. More disability in women than men was also seen in grip force whereas men had more disability than women in SOFI upper extremity. There were no significant differences between women and men in disease activity or disability as measured by VAS pain, GAT, SOFI hand or SOFI lower extremity during the 8-year follow-up.Conclusion: Although disease activity was well managed, disability deteriorated over 8 years with a less favourable course in women than men. Besides controlling disease activity, there is accordingly a need for regular assessments to detect and prevent progressing disability in RA-patients, not only in the early phase of disease, but also over the following years

  • 340.
    Hallert, Eva
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Husberg, Magnus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Kalkan, Almina
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Bernfort, Lars
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Reumatoid artrit är fortfarande en kostsam sjukdom – jämförelse mellan två kohorter2016Ingår i: BestPractice Reumatologi, ISSN 1903-6590, nr 27, s. 14-17Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [sv]

    Sjukdomsaktivitet, funktionsförmåga samt direkta och indirekta kostnader har analyserats i två kohorter av patienter med nydebuterad (≤ 1 år) reumatoid artrit (RA).

    Den första kohorten med 320 patienter (T1) rekryterades 1996–1998 och den andra med 463 patienter (T2) rekryterades 2006–2009. Patienterna har följts regelbundet avseende kliniska och laboratoriemedicinska variabler och har fortlöpande i hälsoekonomienkäter registrerat all sjukvårdskonsumtion och antal dagar med sjukskrivning/sjukersättning samt rapporterat livskvalitet med EQ-5D och EQ-VAS.

  • 341.
    Hallert, Eva
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Husberg, Magnus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Kalkan, Almina
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Bernfort, Lars
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Allergicentrum US.
    Rheumatoid arthritis is still expensive in the new decade: a comparison between two early RA cohorts, diagnosed 1996-98 and 2006-092016Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 45, nr 5, s. 371-378Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES:

    To calculate total costs during the first year after diagnosis in 463 patients with early rheumatoid arthritis (RA) included during 2006-09 (T2) and compare the results with a similar cohort included in 1996-98 (T1).

    METHOD:

    Clinical and laboratory data were collected regularly in both cohorts, and patients completed biannual questionnaires reporting health care utilization and number of days lost from work.

    RESULTS:

    Disease activity was similar in both cohorts T1 and T2 at inclusion. Significant improvements were seen during the first year in both cohorts but were more pronounced in T2. Outpatient care increased and hospitalization decreased in T2 compared with T1. Almost 3% of patients had surgery in both cohorts, but in T2, only women had surgery. Drug costs were higher in T2 than in T1 (EUR 689 vs. EUR 435). In T2, 12% of drug costs were direct costs and 4% were total costs. The corresponding values for T1 were 9% and 3%. In T1, 50% were prescribed disease-modifying anti-rheumatic drugs (DMARDs) at inclusion, compared to T2, where prescription was > 90%. Direct costs were EUR 5716 in T2 and EUR 4674 in T1. Costs for sick leave were lower in T2 than in T1 (EUR 5490 vs. EUR 9055) but disability pensions were higher (EUR 4152 vs. EUR 2139), resulting in unchanged total costs. In T1, direct costs comprised 29% and indirect costs 71% of the total costs. The corresponding values for T2 were 37% and 63%.

    CONCLUSIONS:

    The earlier and more aggressive treatment of RA with traditional DMARDs in T2 resulted in better outcomes compared to T1. Direct costs were higher in T2, partly offset by decreased sick leave, but total costs remained unchanged.

  • 342.
    Hambardzumyan, K.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Hamsten, C.
    Karolinska Inst, Dept Med, Unit Immunol & Allergy, Stockholm, Sweden..
    Idborg, H.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Lourido, Lucia Maria
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Saevarsdottir, S.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    van Vollenhoven, R. F.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands..
    Jakobsson, P. -J
    EVALUATION OF SERUM PROTEIN LEVELS AT BASELINE AS PREDICTORS OF RESPONSE TO METHOTREXATE IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: RESULTS FROM SWEFOT TRIAL POPULATION2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 569-570Artikel i tidskrift (Övrigt vetenskapligt)
  • 343.
    Hambardzumyan, K.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Hamsten, C.
    Karolinska Univ Hosp Solna, Stockholm, Sweden.;Karolinska Inst, Dept Med, Unit Immunol & Allergy, Stockholm, Sweden..
    Idborg, H.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Lourido, Lucia
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Saevarsdottir, S.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Nilsson, P.
    KTH Royal Inst Technol, Sch Biotechnol, SciLife Lab, Affin Prote, Stockholm, Sweden..
    van Vollenhoven, R.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Jakobsson, P.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Evaluation of serum protein levels at baseline as predictors of response to methotrexate in patients with early rheumatoid arthritis: results from the SWEFOT trial population2018Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, s. 31-31Artikel i tidskrift (Övrigt vetenskapligt)
  • 344.
    Han, Jing
    et al.
    Faculty of Public Health, College Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi’an Jiaotong University, Xi’an, China.
    Guo, Xiong
    Faculty of Public Health, College Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi’an Jiaotong University, Xi’an, China.
    Tan, Wuhong
    Faculty of Public Health, College Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi’an Jiaotong University, Xi’an, China.
    Zhang, Feng
    Faculty of Public Health, College Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi’an Jiaotong University, Xi’an, China.
    Liu, Jiangtao
    Faculty of Public Health, College Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi’an Jiaotong University, Xi’an, China.
    Wang, Weizhuo
    Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi’an Jiaotong University, Xi’an, China.
    Xu, Peng
    Department of Orthopaedics Surgery, The Xi’an Red Cross Hospital, Xi’an, China.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland .
    The expression of p-ATF2 involved in the chondeocytes apoptosis of an endemic osteoarthritis, Kashin-Beck disease2013Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 14, artikel-id 209Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The purpose of the study was to understand the function and expression of ATF2 by JNK and p38 signal pathways in the chondrocytes apoptosis of articular cartilage of the Kashin-Beck disease (KBD).

    METHODS: The changes of ATF2, JNK and p38 mRNAs and proteins were investigated between cartilage and chondrocyte as well as KBD and normal. JNK and p38 inhibitors were used as treatments to prevent apoptosis in chondrocytes from KBD patients.

    RESULTS: It was found that the protein levels of p-p38, p-JNK, ATF2 and p-ATF2 increased in KBD human cartilage which is in line with the higher mRNA levels of p38, JNK and ATF2 as compared both with normal cartilage and KBD chondrocytes. In addition, p-ATF2 was only detected in KBD cartilage. Furthermore, JNK inhibitor was more effective than p38 inhibitor in preventing chondrocyte apoptosis at equal concentrations of 10 μM.

    CONCLUSION: These findings indicated the expression of p-ATF2 by JNK and p38 signal pathways involved in the chondrocyte apoptosis in cartilage with KBD.

  • 345.
    Hansson, Claes
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Alenius, Gerd-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    S-Calprotectin (S100A8/S100A9): A Potential Marker of Inflammation in Patients with Psoriatic Arthritis2014Ingår i: Clinical & Developmental Immunology, ISSN 1740-2522, E-ISSN 1740-2530, s. 696415-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To analyse levels of S100A8/S100A9 (calprotectin) and selected cytokines, in blood, in patients with psoriatic arthritis (PsA). Methods. Sixty-five patients with PsA were examined for clinical manifestations and laboratory measurements of S-calprotectin, ESR, hs-CRP, and selected cytokines. Thirty-two patients had mono-/oligoarthritis and 33 had polyarthritis. S-calprotectin, hs-CRP, and cytokines were measured using ELISA, immunoturbidimetry, and multiplex technology (Bio-Plex). Patients with PsA were compared with 31 healthy controls. Results. S-calprotectin and hs-CRP levels were significantly higher in patients with PsA compared with controls (P < 0.001 and P < 0.001, resp.). Patients suffering a polyarthritic disease pattern presented with significantly higher levels of S-calprotectin compared with controls and patients with mono-/oligoarthritis (P < 0.001 and P = 0.017, resp.). The levels of S-calprotectin correlated with hs-CRP (P < 0.001; r(s) = 0.441), swollen joint count (P = 0.002, r(s) = 0.397), and CXCL10 (P = 0.046, r(s) = 0.678) but not with any of the other cytokines evaluated. In multiple logistic regression analysis, S-calprotectin was the only variable significantly associated with psoriatic arthritis (P = 0.002, OR = 1.006, 95% CI = 1.002-1.010). Conclusion. S-calprotectin and hs-CRP levels were significantly higher in patients with PsA. A polyarthritic disease pattern showed higher levels of S-calprotectin thanmono-/oligoarthritis. S-calprotectin is considered a potential marker of disease activity in patients with PsA.

  • 346. Hardt, Uta
    et al.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Gunnarsson, Iva
    Clancy, Robert M
    Petri, Michelle
    Buyon, Jill P
    Silverman, Gregg J
    Svenungsson, Elisabet
    Grönwall, Caroline
    Autoimmune reactivity to malondialdehyde adducts in systemic lupus erythematosus is associated with disease activity and nephritis2018Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 20, artikel-id 36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Immunoglobulin M (IgM) autoreactivity to malondialdehyde (MDA) protein modifications is part of the natural antibody repertoire in health and may have beneficial functions. In contrast, IgG anti-MDA are increased in chronic inflammation and autoimmunity and may instead have pathogenic properties.

    METHODS: Herein, we investigated serum IgG anti-MDA levels by enzyme-linked immunosorbent assay (ELISA) in 398 systemic lupus erythematosus (SLE) patients in the Swedish Karolinska SLE cohort and compared these to findings in 225 US SLE patients from New York University and Johns Hopkins University.

    RESULTS: In two independent cohorts, IgG anti-MDA levels correlated positively with disease activity by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; p < 0.0001, Spearman R = 0.3). Meta-analysis found an odds ratio of 2.7 (confidence interval (CI) 1.9-3.9; p < 0.0001) for high anti-MDA IgG levels with active disease (SLEDAI ≥ 6). Furthermore, IgG anti-MDA correlated directly with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), soluble tumor necrosis factor receptors (sTNFR-1, sTNFR-2), and vascular cell adhesion molecule 1 (VCAM-1) measurements, and inversely with complement factors (C1q, C2, C3, C4). Importantly, IgG anti-MDA levels were significantly elevated in SLE patients with active nephritis (p = 0.0005) and correlated with cystatin C estimated glomerular filtration rate and albuminuria.

    CONCLUSIONS: Elevated IgG anti-MDA in SLE patients was associated with high disease activity, with active lupus nephritis, and with biomarkers of systemic inflammation. This natural antibody reactivity may have potential prognostic utility, and may also actively contribute to pathogenesis.

  • 347.
    Harris, Valerie M.
    et al.
    Univ Oklahoma, Hlth Sci Ctr, Pathol, Oklahoma City, OK USA..
    Cavett, Joshua
    Univ Oklahoma, Hlth Sci Ctr, Med, Oklahoma City, OK USA..
    Kurien, Biji
    Oklahoma Med Res Fdn, Arthrit & Immunol, Oklahoma City, OK 73104 USA..
    Liu, Ke
    Univ Cincinnati & Cincinnati Childre, Cincinnati, OH USA..
    Koelsch, Kristi A.
    Oklahoma Med Res Fdn, Arthrit& Clin Immunol, Okalahoma City, OK USA..
    Radfar, Lida
    Univ Oklahoma, Hlth Sci Ctr, Coll Dent, Oral Diag & Radiol Dept, Oklahoma City, OK USA..
    Lewis, David M.
    Univ Oklahoma, Hlth Sci Ctr, Coll Dent, Dept Oral & Maxillofacial Pathol, Oklahoma City, OK USA..
    Stone, Donald U.
    King Khalid Eye Specialist Hosp, Riyadh, Saudi Arabia..
    Li, Shibo
    Univ Oklahoma, Hlth Sci Ctr, Pediat, Oklahoma City, OK USA..
    Segal, Barbara
    Univ Minnesota, Rheumatol, Minneapolis, MN USA..
    Wallace, Daniel J.
    Cedars Sinai Med Ctr, West Hollywood, CA USA..
    Weisman, Michael H.
    Cedars Sinai Med Ctr, Rheumatol, Los Angeles, CA 90048 USA..
    Kelly, Jennifer A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Alarcon-Riquelme, Marta
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol, Oklahoma City, OK USA..
    Pons-Estel, Bernado
    Hosp Prov Rosario, Rosario, Santa Fe, Argentina..
    Jonsson, Roland
    Broegelmann Res Lab, Bergen, Norway..
    Lu, Xianglan
    Univ Oklahoma, Hlth Sci Ctr, Pediat, Oklahoma City, OK USA..
    Gottenberg, Jacques
    Hautepierre, Strasbourg, France..
    Anaya, Juan-Manuel
    CIB Rosario Univ, Cell Biol & Immunogenet, Medellin, Colombia..
    Cunninghame-Graham, Deborah S.
    Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England..
    Keystone, Edward C.
    Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada..
    Huang, Andrew J. W.
    Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA..
    Brennan, Michael T.
    Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA..
    Hughes, Pamela
    Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA..
    Illei, G.
    NIDCR, Sjogrens Clin, NIH, Bethesda, MD USA..
    Miceli, Corinne
    Bykerk, V. P.
    Univ Toronto, Toronto, ON, Canada..
    Hirschfield, Gideon
    Univ Birmingham, Coll Med & Dent Sci, Inst Biomed Res, Ctr Liver Res,Sch Immun & Infect, Birmingham, W Midlands, England..
    Xie, Gang
    Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada..
    Ng, Wan-Fai
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England..
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Eriksson, Per
    Linkoping Univ Hosp, Rheumatol Clin, S-58185 Linkoping, Sweden..
    Omdal, Roald
    Clin Immunol Unit, Dept Internal Med, Stavanger, Norway..
    Rhodus, Nelson L.
    Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA..
    Rischmueller, Maureen
    Queen Elizabeth Hosp, Rheumatol, Adelaide, SA, Australia..
    Rohrer, Michael D.
    Univ Minnesota, Sch Dent, Hard Tissue Res Lab, Minneapolis, MN 55455 USA..
    Wahren-Herlenius, Marie
    Expt Rheumatol Unit, Dept Med, Solna, Sweden..
    Witte, Torsten
    Hannover Med Sch, Dept Immunol & Rheumatol, Hannover, Germany..
    Mariette, Xavier
    Univ Paris Sud, Hop Univ Paris Sud, AP HP, Paris, France..
    Lessard, Christopher
    Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA..
    Harley, John B.
    Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH 45229 USA..
    Sivils, Kathy L.
    Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA..
    Scofield, Robert Hal
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.;US Dept Vet Affairs Med Ctr, Oklahoma City, OK USA..
    Klinefelter's Syndrome (47,XXY) Among Men with Sjogren's Syndrome2015Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, nr Suppl. 10, artikel-id 648Artikel i tidskrift (Övrigt vetenskapligt)
  • 348.
    Harris, Valerie M.
    et al.
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, USA.
    Sharma, Rohan
    University of Oklahoma,USA; Department Vet Affairs Medical Centre, OK USA.
    Cavett, Joshua
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, USA.
    Kurien, Biji T.
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, USA; Department Vet Affairs Medical Centre, OK USA.
    Liu, Ke
    Cincinnati Childrens Hospital Medical Centre, USA; University of Cincinnati, USA.
    Koelsch, Kristi A.
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, USA; Department Vet Affairs Medical Centre, USA.
    Rasmussen, Astrid
    Oklahoma Medical Research Fdn, USA.
    Radfar, Lida
    University of Oklahoma, USA.
    Lewis, David
    University of Oklahoma, USA.
    Stone, Donald U.
    University of Oklahoma, USA; University of Oklahoma, USA.
    Erick Kaufman, C.
    University of Oklahoma, USA.
    Li, Shibo
    University of Oklahoma, USA.
    Segal, Barbara
    University of Minnesota, USA.
    Wallace, Daniel J.
    Cedars Sinai Medical Centre, USA.
    Weisman, Michael H.
    Cedars Sinai Medical Centre, USA.
    Venuturupalli, Swamy
    Cedars Sinai Medical Centre, USA.
    Kelly, Jennifer A.
    Oklahoma Medical Research Fdn, USA.
    Alarcon-Riquelme, Marta E.
    Oklahoma Medical Research Fdn, USA; University of Granada, Spain.
    Pons-Estel, Bernardo
    Sanat Parque, Argentina.
    Jonsson, Roland
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Lu, Xianglan
    University of Oklahoma, USA.
    Gottenberg, Jacques-Eric
    Strasbourg University, France.
    Anaya, Juan-Manuel
    University of Rosario, Colombia.
    Cunninghame-Graham, Deborah S.
    Kings Coll London, England.
    Huang, Andrew J. W.
    University of Minnesota, USA.
    Brennan, Michael T.
    Carolinas Medical Centre, USA.
    Hughes, Pamela
    University of Minnesota, MN USA.
    Alevizos, Ilias
    National Institute Dent and Craniofacial Research, MD USA.
    Miceli-Richard, Corinne
    University of Paris 11, France.
    Keystone, Edward C.
    Mt Sinai Hospital, Canada; University of Toronto, Canada.
    Bykerk, Vivian P.
    Hospital Special Surg, NY USA.
    Hirschfield, Gideon
    University of Birmingham, England.
    Xie, Gang
    University of Toronto, Canada.
    Ng, Wan-Fai
    Newcastle University, England.
    Nordmark, Gunnel
    Uppsala University, Sweden.
    Magnusson Bucher, Sara
    Örebro University Hospital, Sweden.
    Eriksson, Per
    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.
    Omdal, Roald
    Stavanger University Hospital, Norway.
    Rhodus, Nelson L.
    University of Minnesota, USA.
    Rischmueller, Maureen
    Queen Elizabeth Hospital, Australia; University of Adelaide, Australia.
    Rohrer, Michael
    University of Minnesota, USA.
    Wahren-Herlenius, Marie
    Karolinska Institute, Sweden.
    Witte, Torsten
    Hannover Medical Sch, Germany.
    Mariette, Xavier
    University of Paris 11, France.
    Lessard, Christopher J.
    Oklahoma Medical Research Fdn, USA.
    Harley, John B.
    Cincinnati Childrens Hospital Medical Centre, USA; University of Cincinnati, OH USA; Department Vet Affairs Medical Centre, OH USA.
    Sivils, Kathy L.
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, OK 73190 USA.
    Scofield, R. Hal
    Oklahoma Medical Research Fdn, USA; University of Oklahoma, OK 73190 USA; University of Oklahoma, OK 73190 USA; Department Vet Affairs Medical Centre, OK USA.
    Klinefelters syndrome (47,XXY) is in excess among men with Sjogrens syndrome2016Ingår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 168, s. 25-29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Primary Sjogrens syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelters syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47)0(Y, p = 0.0012 by Fishers exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fishers exact test p = NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA. Published by Elsevier Inc.

  • 349. Harris, Valerie M.
    et al.
    Sharma, Rohan
    Cavett, Joshua
    Kurien, Biji T
    Liu, Ke
    Koelsch, Kristi A
    Rasmussen, Astrid
    Radfar, Lida
    Lewis, David
    Stone, Donald U
    Kaufman, C Erick
    Li, Shibo
    Segal, Barbara
    Wallace, Daniel J
    Weisman, Michael H
    Venuturupalli, Swamy
    Kelly, Jennifer A
    Alarcon-Riquelme, Marta E
    Pons-Estel, Bernardo
    Jonsson, Roland
    Lu, Xianglan
    Gottenberg, Jacques-Eric
    Anaya, Juan-Manuel
    Cunninghame-Graham, Deborah S
    Huang, Andrew J W
    Brennan, Michael T
    Hughes, Pamela
    Alevizos, Ilias
    Miceli-Richard, Corinne
    Keystone, Edward C
    Bykerk, Vivian P
    Hirschfield, Gideon
    Xie, Gang
    Ng, Wan-Fai
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bucher, Sara Magnusson
    Eriksson, Per
    Omdal, Roald
    Rhodus, Nelson L
    Rischmueller, Maureen
    Rohrer, Michael
    Wahren-Herlenius, Marie
    Witte, Torsten
    Mariette, Xavier
    Lessard, Christopher J
    Harley, John B
    Sivils, Kathy L
    Scofield, R Hal
    Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome2016Ingår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 168, s. 25-29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Primary Sjögren's syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelter's syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47,XXY, p=0.0012 by Fisher's exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fisher's exact test p=NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA.

  • 350.
    Heaney, Alice
    et al.
    England.
    McKenna, Stephen P.
    England.
    Hagell, Peter
    Högskolan Kristianstad, Fakulteten för hälsovetenskap, Forskningsmiljön PRO-CARE, Patient Reported Outcomes - Clinical Assessment Research and Education. Högskolan Kristianstad, Forskningsplattformen för Hälsa i samverkan. Högskolan Kristianstad, Fakulteten för hälsovetenskap, Avdelningen för sjuksköterskeutbildningarna och integrerad hälsovetenskap.
    Sengupta, Raj
    England.
    Using Rasch analysis to determine the internal validity of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)2018Ingår i: International Conference on Probabilistic Models for Measurement, 2018Konferensbidrag (Övrigt vetenskapligt)
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