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  • 1.
    Adeteg, Sandra
    et al.
    Örebro University, School of Health and Medical Sciences.
    Bergman, Eva-Lena
    Örebro University, School of Health and Medical Sciences.
    Att vara ung vuxen med reumatisk sjukdom och leva med kronisk smärta och trötthet: En kvalitativ intervjustudie2009Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syftet med studien var att fånga in hur trötthet och smärta påverkar vardagen för unga vuxna med reumatisk sjukdom.

    Metoden är kvalitativ och för datainsamlingen gjordes semistrukturerade intervjuer. Materialet transkriberades transkriberades i sin helt och när det var klart påbörjades analysering av det som framkommit. I analysen sökte vi efter meningsbärande enheter och försökte ordna dem i kategorier och underkategorier.

    Resultatet visar att sjukdomen har en stor påverkan på våra informanters liv, men att de också har bra strategier för att kunna leva med sjukdomen. Det visar också på att även om strategierna är bra och de vet hur de ska hantera sjukdomen så stöter de på hinder, till exempel har skolgången blivit negativt påverkad för de flesta av informanterna. Något som visat sig vara extra viktigt har varit vännerna och det sociala nätverket. Alla informanter har på ett eller annat sätt verkligen understrykt betydelsen av vänner som är förstående och som på det sättet hjälper till att hitta det positiva med livet.

    Slutsatsen som kan dras utifrån detta arbete är att vara ung och ha en reumatisk sjukdom är något som påverkar hela livet. Vi har sett på informanterna i studien att trots detta flyter livet på och de lyckas i de flesta fall att få balans mellan aktivitet och vila. Just denna balans är mycket viktig.

     

  • 2. Agca, R.
    et al.
    Heslinga, S. C.
    Rollefstad, S.
    Heslinga, M.
    McInnes, B.
    Peters, M. J. L.
    Kvien, T. K.
    Dougados, M.
    Radner, H.
    Atzeni, F.
    Primdahl, J.
    Södergren, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Wållberg Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    van Rompay, J.
    Zabalan, C.
    Pedersen, T. R.
    Jacobsson, L.
    de Vlam, K.
    Gonzalez-Gay, M. A.
    Semb, A. G.
    Kitas, G. D.
    Smulders, Y. M.
    Szekanecz, Z.
    Sattar, N.
    Symmons, D. P. M.
    Nurmohamed, M. T.
    EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, no 1, 17-28 p.Article, review/survey (Refereed)
    Abstract [en]

    Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

  • 3. Agmon-Levin, Nancy
    et al.
    Damoiseaux, Jan
    Kallenberg, Cees
    Sack, Ulrich
    Witte, Torsten
    Herold, Manfred
    Bossuyt, Xavier
    Musset, Lucille
    Cervera, Ricard
    Plaza-Lopez, Aresio
    Dias, Carlos
    Sousa, Maria Jose
    Radice, Antonella
    Eriksson, Catharina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Hultgren, Olof
    Viander, Markku
    Khamashta, Munther
    Regenass, Stephan
    Coelho Andrade, Luis Eduardo
    Wiik, Allan
    Tincani, Angela
    Ronnelid, Johan
    Bloch, Donald B.
    Fritzler, Marvin J.
    Chan, Edward K. L.
    Garcia-De la Torre, I.
    Konstantinov, Konstantin N.
    Lahita, Robert
    Wilson, Merlin
    Vainio, Olli
    Fabien, Nicole
    Sinico, Renato Alberto
    Meroni, Pierluigi
    Shoenfeld, Yehuda
    International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies2014In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, no 1, 17-23 p.Article in journal (Refereed)
    Abstract [en]

    Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.

  • 4. Ahlin, Erik
    et al.
    Elshafei, Amir
    Nur, Musa
    El Safi, Sayda Hassan
    Ronnelid, Johan
    Elghazali, Gehad
    Retraction: Anti-citrullinated peptide antibodies and rheumatoid factor in Sudanese patients with Leishmania donovani infection (vol 51, pg 579, 2011)2014In: Revista Brasileira de Reumatologia, ISSN 0482-5004, E-ISSN 1809-4570, Vol. 54, no 3, 255-255 p.Article in journal (Refereed)
  • 5.
    Ahlstrand, Inger
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Rehabilitation. Jönköping University, School of Health and Welfare, HHJ. ADULT.
    Vaz, Sharmila
    School of Occupational Therapy & Social Work, CHIRI, Curtin University, Perth, WA, Australia.
    Falkmer, Torbjörn
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Rehabilitation. Jönköping University, School of Health and Welfare, HHJ. CHILD. Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Thyberg, Ingrid
    Department of Rheumatology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Björk, Mathilda
    Department of Rheumatology and Department of Social and Welfare Studies, Linköping University, Norrköping, Sweden.
    Self-efficacy and pain acceptance as mediators of the relationship between pain and performance of valued life activities in women and men with rheumatoid arthritis2017In: Clinical Rehabilitation, ISSN 0269-2155, E-ISSN 1477-0873, Vol. 31, no 6, 824-834 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study whether personal factors (self-efficacy and pain acceptance) mediate the relationship between pain and performance of valued life activities in persons with rheumatoid arthritis.

    METHODS: Persons with rheumatoid arthritis for at least four years (n = 737; 73% women) answered a questionnaire measuring self-efficacy, pain acceptance, performance of valued life activities, and self-rated pain. Relationships among these constructs were explored using univariate and multivariate analyses. Structural equation modelling was then used to examine the mediational role of personal factors on the relationship between pain and performance of valued life activities.

    RESULTS: A direct negative association between pain and performance of valued life activities was identified (Beta = .34, P < .001). This suggests that people with rheumatoid arthritis who had higher levels of pain has increased difficulties in performing valued life activities. Self-efficacy and activity engagement component of pain acceptance mediated the relationship between pain and performance of valued life activities, however the pain willingness component of pain acceptance did not influence participation in valued life activities.

    CONCLUSION: These findings highlight the importance of considering personal factors, such as pain acceptance and self-efficacy, in facilitating participation in valued life activities.

  • 6.
    Ahlstrand, Inger
    et al.
    School of Health and Welfare, Jönköping University, Jönköping, Sweden.
    Vaz, Sharmila
    School of Occupational Therapy & Social Work, CHIRI, Curtin University, Perth, WA, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. School of Health and Welfare, Jönköping University, Jönköping, Sweden.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Björk, Mathilda
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Rehabilitation Center.
    Self-efficacy and pain acceptance as mediators of the relationship between pain and performance of valued life activities in women and men with rheumatoid arthritis2017In: Clinical Rehabilitation, ISSN 0269-2155, E-ISSN 1477-0873, Vol. 31, no 6, 824-834 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study whether personal factors (self-efficacy and pain acceptance) mediate the relationship between pain and performance of valued life activities in persons with rheumatoid arthritis.

    METHODS: Persons with rheumatoid arthritis for at least four years (n = 737; 73% women) answered a questionnaire measuring self-efficacy, pain acceptance, performance of valued life activities, and self-rated pain. Relationships among these constructs were explored using univariate and multivariate analyses. Structural equation modelling was then used to examine the mediational role of personal factors on the relationship between pain and performance of valued life activities.

    RESULTS: A direct negative association between pain and performance of valued life activities was identified (Beta = .34, P < .001). This suggests that people with rheumatoid arthritis who had higher levels of pain has increased difficulties in performing valued life activities. Self-efficacy and activity engagement component of pain acceptance mediated the relationship between pain and performance of valued life activities, however the pain willingness component of pain acceptance did not influence participation in valued life activities.

    CONCLUSION: These findings highlight the importance of considering personal factors, such as pain acceptance and self-efficacy, in facilitating participation in valued life activities.

  • 7.
    Ajeganova, Sofia
    et al.
    Karolinska Inst, Dept Med Huddinge, S-14186 Stockholm, Sweden..
    Tesfa, Daniel
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, S-14186 Stockholm, Sweden.;Roche AB, Med Affairs, S-10074 Stockholm, Sweden..
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Fadeel, Bengt
    Karolinska Inst, Inst Environm Med, Unit Mol Toxicol, S-17177 Stockholm, Sweden..
    Vedin, Inger
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, S-14186 Stockholm, Sweden..
    Zignego, Anna Linda
    Univ Florence, Ctr Syst Manifestat Hepatitis Viruses, Dept Internal Med, I-50134 Florence, Italy..
    Palmblad, Jan
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, S-14186 Stockholm, Sweden..
    Effect of FCGR polymorphism on the occurrence of late-onset neutropenia and flare-free survival in rheumatic patients treated with rituximab2017In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, 44Article in journal (Refereed)
    Abstract [en]

    Background: The causes and mechanisms of late-onset neutropenia (LON) following rituximab treatment in patients with rheumatic diseases are not known. In this study, we aimed to investigate the role of established Fc gamma receptor gene (FCGR) polymorphisms and B-cell-activating factor (BAFF) gene promoter polymorphisms for the development of LON and for the efficacy of rituximab in patients with rheumatic diseases. Methods: A single-center case-control retrospective study was nested in a cohort of 214 consecutive patients with rheumatic diseases treated with rituximab. Eleven patients presented with LON. Fifty non-LON control subjects were matched by diagnosis, age, sex, and treatments. Single-nucleotide polymorphisms of FCGR (FCGR2A 131H/R, FCGR2B 232I/T, FCGR3A 158V/F) and BAFF promoter polymorphism -871C/T were analyzed with polymerase chain reaction-based techniques, and serum immunoglobulin M (IgM) and BAFF levels were analyzed by enzyme-linked immunosorbent assay. Flare-free survival was related to LON occurrence and polymorphisms. Results: The FCGR3A V allele, but not other FCGR polymorphisms, correlated with the occurrence of LON; each V allele conferred a fourfold increased OR for LON (p = 0.017). FCGR3A 158V/V and presentation with LON were associated with a longer flare-free survival (p = 0.023 and p = 0.031, respectively). FCGR3A 158V/V was related to lower IgM levels (p = 0.016). Serum BAFF levels showed no relationship with LON and BAFF -871C/T promoter polymorphism. There was a tendency toward longer flare-free survival in patients with the BAFF -871T/T allotype compared with the C/T or C/C allotypes (p = 0.096). Conclusions: The results of the present study suggest that presentation with LON may be a result of the intrinsic efficacy of rituximab in patients with rheumatic diseases. LON could indicate a longer biological and therapeutic activity of rituximab modulated by a certain genotypic polymorphism: the high-affinity FCGR3A V allele. This genotype and the occurrence of LON are both related to longer flare-free survival, suggestive of common mechanisms for LON and duration of response to rituximab. The role of the BAFF -871C/T promoter polymorphism in LON occurrence is unclear.

  • 8. Alarcón-Riquelme, Marta E.
    et al.
    Marañón Lizana, Concepción
    Varela Hernández, Nieves
    Delgado-Vega, Angélica M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    La Etiopatogenia en el Lupus Eritematoso Sistémico2013In: LUPUS ERITEMATOSO SISTÉMICO: Aspectos Clínicos y Terapéuticos, Rosario, Argentina: Carlos Antonio Battagliotti , 2013, 1, 65-85 p.Chapter in book (Refereed)
  • 9.
    Alberdi-Saugstrup, Mikel
    et al.
    Rigshosp, Dept Pediat & Adolescent Med, Copenhagen Univ Hosp, Copenhagen, Denmark.;Naestved Hosp, Dept Pediat, Naestved, Region Zealand, Denmark.;Rigshosp, Inst Inflammat Res, Copenhagen Univ Hosp, Copenhagen, Denmark..
    Zak, Marek
    Rigshosp, Dept Pediat & Adolescent Med, Copenhagen Univ Hosp, Copenhagen, Denmark..
    Nielsen, Susan
    Rigshosp, Dept Pediat & Adolescent Med, Copenhagen Univ Hosp, Copenhagen, Denmark..
    Herlin, Troels
    Aarhus Univ Hosp, Dept Pediat, Aarhus, Denmark..
    Nordal, Ellen
    Univ Hosp North Norway, Dept Pediat, Tromso, Norway..
    Berntson, Lillemor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Fasth, Anders
    Univ Gothenburg, Dept Pediat, Gothenburg, Sweden..
    Rygg, Marite
    Norwegian Univ Sci & Technol, Dept Lab Med Childrens & Womens Hlth, Trondheim, Norway.;St Olavs Hosp, Dept Pediat, Trondheim, Norway..
    Müller, Klaus
    Rigshosp, Dept Pediat & Adolescent Med, Copenhagen Univ Hosp, Copenhagen, Denmark.;Rigshosp, Inst Inflammat Res, Copenhagen Univ Hosp, Copenhagen, Denmark..
    High-sensitive CRP as a predictive marker of long-term outcome in juvenile idiopathic arthritis2017In: Rheumatology International, ISSN 0172-8172, E-ISSN 1437-160X, Vol. 37, no 5, 695-703 p.Article in journal (Refereed)
    Abstract [en]

    To evaluate whether C-reactive protein (CRP), including variation within the normal range, is predictive of long-term disease outcome in Juvenile Idiopathic Arthritis (JIA). Consecutive patients with newly diagnosed JIA were included prospectively from defined geographic areas of the Nordic countries from 1997 to 2000. Inclusion criteria were availability of a baseline serum sample within 12 months after disease onset and 8-year clinical assessment data. Systemic onset JIA was not included. CRP was measured by high-sensitive ELISA (detection limit of 0.2 mg/l). One hundred and thirty participants with a median follow-up time of 97 months (range 95-100) were included. At follow-up, 38% of the patients were in remission off medication. Absence of remission was associated with elevated level of CRP at baseline (odds ratio (OR) 1.33, confidence interval (CI) 1.08-1.63, p = 0.007). By applying a cutoff at the normal upper limit (> 10 mg/l), the risk of not achieving remission was increased to an OR of 8.60 (CI 2.98-24.81, p < 0.001). Variations of CRP within the normal range had no predictive impact on disease activity at follow-up. Baseline levels of ESR were available in 80 patients (61%) and elevated ESR was associated with absence of remission in a multivariable logistic regression analysis (OR 2.32, CI 1.35-4.00, p = 0.002). This results of this study indicate that baseline CRP concentrations above 10 mg/l are predictive of a poor outcome at 8-year follow-up. We could not demonstrate any predictive value of CRP variations within the normal range.

  • 10.
    Alenius, G M
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Jonsson, S
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Jonsson, S W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Ny, A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Dahlqvist, Solbritt Rantapää
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Matrix metalloproteinase 9 (MMP-9) in patients with psoriatic arthritis and rheumatoid arthritis2001In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 19, no 6, 760-760 p.Article in journal (Refereed)
  • 11.
    Alenius, Gerd-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Eriksson, C
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Interleukin-6 and soluble interleukin-2 receptor alpha-markers of inflammation in patients with psoriatic arthritis?2009In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 27, no 1, 120-123 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate a possible systemic effect of joint inflammation in contrast to skin disease only, by measuring IL-6 and IL-2sRalpha. METHODS: Two hundred and nineteen patients (111 male / 108 female, age 50.4+/-14.5 yrs (mean+/-SD)) with psoriasis were clinically and laboratory examined. 134 patients had inflammatory joint manifestations defined as peripheral arthritis and/or axial disease, of whom 37 had measurable inflammation, defined as ESR >25 mm/h and/or CRP >15 mg/L. RESULTS: Interleukin-6 was significantly higher in patients with joint disease and measurable inflammation ((median, Q1-Q3) 4.07, 0.92-14.60), and in patients without measured inflammation (1.22, 0.70-3.46), compared to patients with skin disease only (0.70, 0.70-1.73, p<0.001 and p=0.002 respectively). The difference between the two groups of patients with inflammatory joint manifestations was significant (p=0.001). The levels of IL-6 correlated with the actual number of joints affected with arthritis (p<0.001; rs=0.248), ESR (p<0.001; rs=0.459), CRP (p<0.001; rs=0.314) and IL-2sRalpha (p=0.002; rs=0.210). The levels of IL-2sRalpha. did not differ between the 3 groups. CONCLUSION: In this study, IL-6 was significantly higher in patients with psoriasis and inflammatory joint disease with or without routine measurable inflammatory activity compared with patients having psoriasis of the skin. We found that patients with psoriasis and joint inflammation may have systemic effects that could be captured by serum measurements of IL-6. Soluble IL-2Ralpha was not a marker of inflammation in this study.

  • 12.
    Alenius, Gerd-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Husmark, Tomas
    Theander, Elke
    Larsson, Per
    Geijer, Mats
    Teleman, Annika
    Lindqvist, Ulla R. C.
    Rheumatoid Arthritis, a More Severe Disease Than Psoriatic Arthritis?: A Comparison Of Disease Activity In Patients With Psoriatic Arthritis and Rheumatoid Arthritis From The Swedish Early Psoriatic Arthritis Registry (SwePsA) and The Swedish Rheumatology Registry For Early Rheumatoid Arthritis (SRR)2013In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, no Special issue, Supplement 10, S150-S150, Meeting Abstract: 346 p.Article in journal (Other academic)
  • 13.
    Alenius, Gerd-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jidell, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nordmark, L
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden2002In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 21, no 5, 357-362 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to identify potential markers of aggressive joint manifestations and HLA associations in patients with psoriatic arthritis (PsA) in northern Sweden. Patients with PsA were examined clinically, with laboratory tests and radiologically. The classification of the disease was based on peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly increased in PsA patients. Univariate analyses suggest that the HLA antigens B37, B62 and some clinical variables were associated with disease course. However, in multivariate analyses distal interphalangeal joint affliction and polyarticular manifestations were the only variables remaining significantly associated with irreversible joint destruction or deformity. There were no significant effects of HLA antigens. In this cross-sectional study, clinical manifestations were more reliable predictors of aggressive joint damage than were specific HLA antigens. However, HLA antigens seemed to modify the expression of the joint disease rather than being involved in joint disease susceptibility.

  • 14.
    Ali, Abukar
    University of Skövde, School of Life Sciences.
    Time window of TNF-a in innate immunity against staphylococcal infection2010Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Staphylococcus aureus (S. aureus) is responsible for many human diseases including septic arthritis and sepsis shock. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in inflammation and produced mainly by macrophages and monocytes. It is believed to be involved in pathogenesis of septic arthritis. Time window of TNF-a in innate immunity against staphylococcal infection was studied in this project.

    Two experiments were carried out: In the first experiment mice were infected with a low dose (8x106cfu/mouse) of S. aureus to induce septic arthritis whereas in the second experiment the mice were infected with a higher dose (8x107cfu/mouse) of S. aureus to induce sepsis shock. All mice were divided into three groups. The first group was treated with anti-TNF-α 20 minutes after infection. The second group was treated with the anti-TNF-α three days after infection. The third group served as control and was injected with PBS instead of anti-TNF-α. The mice were regularly weighed and signs of arthritis and mortality were recorded. Two weeks after inoculation bacteria viable counts in different organs was done, as well as histopathological assessment of joints and measurement of cytokines in blood.

    We have observed that mice treated with anti-TNF-α had less severe arthritis and also less mortality. However, they had more bacteria accumulated in the kidneys and lost more weight compared to the control group. The results were mostly seen in the group early treated with TNF-α, compared to the late treated group.

    We conclude that anti-TNF-α might be potentially used as a therapy against septic arthritis and sepsis shock. This should be combined with antibiotics to eliminate the bacteria while the anti-TNF-α reduces the severity of the inflammation and thus reduce the risk of permanent joint destruction and mortality. We can conclude that blocking TNF-α early on is essential in order to get the best results.

  • 15.
    Alimohammadi, Mohammad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Scalp necrosis as a late sign of giant-cell arteritis2013In: Case reports in immunology, ISSN 2090-6609, Vol. 2013, 231565Article in journal (Refereed)
    Abstract [en]

    Retinal infarction and scalp necrosis are described as unusual but devastating complications of giant-cell arteritis. We report a patient with this rare complication and emphasize the importance of timely diagnosis and treatment of giant-cell arteritis.

  • 16. Allum, Fiona
    et al.
    Shao, Xiaojian
    Guénard, Frédéric
    Simon, Marie-Michelle
    Busche, Stephan
    Caron, Maxime
    Lambourne, John
    Lessard, Julie
    Tandre, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hedman, Åsa K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kwan, Tony
    Ge, Bing
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    McCarthy, Mark I
    Deloukas, Panos
    Richmond, Todd
    Burgess, Daniel
    Spector, Timothy D
    Tchernof, André
    Marceau, Simon
    Lathrop, Mark
    Vohl, Marie-Claude
    Pastinen, Tomi
    Grundberg, Elin
    Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants2015In: Nature Communications, ISSN 2041-1723, Vol. 6, 7211Article in journal (Refereed)
    Abstract [en]

    Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.

  • 17. Almehed, Katarina
    et al.
    d'Elia, Helena Forsblad
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Bokarewa, Maria
    Carlsten, Hans
    Role of resistin as a marker of inflammation in systemic lupus erythematosus.2008In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 10, no 1, R15- p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Resistin is a cystein-rich secretory adipokine. It is proposed to have proinflammatory properties in humans. The aim of this study was to determine associations between serum levels of resistin and markers of inflammation and bone mineral density (BMD) in female patients with systemic lupus erythematosus (SLE).

    METHODS: One hundred sixty-three female patients with SLE (20 to 82 years old) were examined in a cross-sectional study. Venous blood samples were analyzed for resistin, erythrocyte sedimentation rate (ESR), C-reactive protein, creatinine, fasting lipids, complements, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, sIL-6R (soluble IL-6 receptor), ICTP (C-terminal telopeptide of type I collagen), and PINP (N-terminal propeptide of type I procollagen). Simple and multiple regression analyses as well as logistic regression analyses were performed. Resistin in serum was compared with 42 healthy female controls with respect to age.

    RESULTS: Serum resistin levels in controls were similar to those of patients with SLE. Markers of inflammation and current dose of glucocorticosteroids correlated positively to resistin in serum. Markers of renal function, number of prevalent vertebral fractures, and BMD were also significantly associated with resistin. In a multiple regression model, ESR, creatinine, C3, current glucocorticosteroid dose, high-density lipoprotein, and BMD radius remained significantly associated with resistin. In logistic regression analyses with resistin as the independent variable, a significant association was found with ESR (normal or elevated) but not with S-creatinine or z score for hip and radius total.

    CONCLUSION: Although resistin measurements did not differ between patients and controls, resistin was clearly associated with general inflammation, renal disease, treatment with glucocorticosteroids, and bone loss. We hypothesize that resistin has proinflammatory and disease-promoting properties in SLE. Further studies are needed to elucidate the mechanism behind these associations.

  • 18. Almehed, Katarina
    et al.
    Hetényi, Szabolcs
    Ohlsson, Claes
    Carlsten, Hans
    Forsblad-d'Elia, Helena
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Prevalence and risk factors of vertebral compression fractures in female SLE patients.2010In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 12, no 4, R153- p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Our objective was to determine the frequency of and factors associated with prevalent vertebral compression fractures in female systemic lupus erythematosus (SLE) patients attending rheumatologists in western Sweden.

    METHODS: In this cross sectional study 150 women were included. They were examined with x-ray of thoracic and lumbar spine (Th4 to L4). A reduction of at least 20% of any vertebral height, assessed by Genant's semiquantitative method, was defined as a fracture. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA).

    RESULTS: Median patient age was 47 years (20 to 82) and disease duration 11 years (1 to 41). Only 6 (4%) women had a history of clinical compressions whereas 43 (29%) had at least one radiological fracture each. The patients with at least one fracture at any site were characterized by older age (P < 0.001), being postmenopausal (P < 0.01), higher Systemic Lupus International Collaborative Clinics Damage Index (P < 0.05), lower BMD total hip and femoral neck (P < 0.05), more peripheral fractures (P < 0.01), medication with bisphosphonates (P <0.05) and calcium and vitamin D3 (P < 0.05). There were no significant differences regarding current or cumulative glucocorticosteroid dose between the groups. In logistic regression analyses high age remained as a risk factor of at least one vertebral fracture at any site whereas low BMD in total hip was associated with vertebral fracture in the lumbar spine.

    CONCLUSIONS: Radiological compression fractures are common but seldom diagnosed in SLE patients. High age and low BMD in total hip, but not in spine, was associated with vertebral fractures.

  • 19.
    Almroth, Gabriel
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Lönn, Johanna
    Örebro Universitet, Sweden.
    Uhlin, Fredrik
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Physiology, County Hospital, Kalmar, Sweden.
    Andersson, Bengt Andersson
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Hahn-Zoric, Mirjana
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Sclerostin, TNF-alpha and Interleukin-18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients2016In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 83, no 1, 58-63 p.Article in journal (Refereed)
    Abstract [en]

    Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNF-alpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.

  • 20. Ambrosi, Aurelie
    et al.
    Salomonsson, Stina
    Eliasson, Håkan
    Zeffer, Elisabeth
    Dzikaite, Vijole
    Bergman, Gunnar
    Fernlund, Eva
    Theander, Elke
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhman, Annika
    Skogh, Thomas
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Fored, Michael
    Blomqvist, Paul
    Ekbom, Anders
    Lindström, Ulla
    Melander, Mats
    Winqvist, Ola
    Gadler, Fredrik
    Jonzon, Anders
    Sonesson, Sven-Erik
    Wahren-Herlenius, Marie
    Influence of season of birth and maternal age in the development of congenital heart block in anti-Ro-SSA/La-SSB positive pregnancies2010In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 72, no 3, 265- p.Article in journal (Refereed)
  • 21. Andersen, Grethe N.
    et al.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Wikberg, Jarl E. S.
    The Melanocortin System: A New and Important Actor on the Scene of Systemic Sclerosis2011In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 63, no 10, S908-S908 p.Article in journal (Refereed)
  • 22.
    Andersen, Grethe Neumann
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Caidahl, Kenneth
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Kazzam, Elsadig
    Petersson, Ann-Sofi
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis: findings with the soluble adhesion molecules E-selectin, intercellular adhesion molecule 1, and vascular adhesion molecule 12000In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 43, no 5, 1085-1093 p.Article in journal (Refereed)
    Abstract [en]

    Objective To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease.

    Methods We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting.

    Results Plasma nitrate and 24-hour-urinary-excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate.

    Conclusion NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.

  • 23.
    Andersen, Grethe Neumann
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Kazzam, Elsadig
    Mälar Hospital, Eskilstuna, Sweden.
    Nyberg, Gunnar
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Klintland, Natalia
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Petersson, Ann-Sofi
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Caidahl, Kenneth
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Assessment of vascular function in systemic sclerosis: indications of the development of nitrate tolerance as a result of enhanced endothelial nitric oxide production2002In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 46, no 5, 1324-1332 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the relationship between endothelium-dependent and endothelium-independent functions and the stiffness of conduit arteries as well as levels of endothelial activation markers in patients with systemic sclerosis (SSc).

    METHODS: Endothelium-dependent (i.e., flow-mediated) and endothelium-independent (i.e., nitroglycerin-induced) dilation of the brachial artery was measured as the percentage of change from baseline (FMD% and NTG%, respectively) in 24 SSc patients and 24 age- and sex-matched healthy controls by high-resolution ultrasound imaging. The maximum increase in systolic pressure per unit of time (dP/dt(max)), as a measure of arterial wall stiffness, was assessed in the radial artery by pulse applanation tonometry. Plasma nitrate, the most important metabolite of nitric oxide, and 24-hour urinary excretion of nitrate were measured by gas chromatography mass spectrometry. Soluble E-selectin and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay.

    RESULTS: Brachial artery FMD% and NTG% did not differ between SSc patients and controls. Radial artery dP/dt(max) was significantly increased in the patients and correlated significantly with elevated levels of plasma nitrate and sVCAM-1. Twenty-four-hour urinary nitrate excretion tended to be elevated. Brachial artery NTG% was significantly inversely correlated with levels of plasma nitrate and soluble endothelial adhesion molecules.

    CONCLUSION: The ability of the brachial arteries to dilate in response to hyperemia and nitroglycerin challenge is preserved in SSc. Stiffness of the radial artery is increased, however. Endothelial activation seems to determine the extent of the brachial artery NTG% and the radial artery dP/dt(max). The data are compatible with the hypothesis that nitrate tolerance is present in the vascular smooth muscle cells of the brachial artery wall in SSc.

  • 24. Andersen, M.
    et al.
    Olesen, M. K.
    Nagaev, I.
    Nagaeva, O.
    Wikberg, Jarl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Mincheva-Nilsson, L.
    Andersen, G. N.
    Adalimumab (Humira (R)) normalizes melanocortin receptor subtype 2, 3, and 4 expression in CD8+, CD14+, and CD19+leucocyte subsets in rheumatoid arthritis2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, 25-26 p.Article in journal (Other academic)
  • 25.
    Andersson, H. Ingemar
    et al.
    Kristianstad University, Department of Health Sciences.
    Leden, Ido
    Reumatologsektionen, Medicinska kliniken, Centralsjukhuset Kristianstad.
    Att möta individer med smärta från rörelseapparaten: tidiga överväganden i primärvård2000In: Allmänmedicin, Vol. 21, no 6, 228-231 p.Article in journal (Other academic)
  • 26.
    Andersson, H. Ingemar
    et al.
    Kristianstad University, Department of Health Sciences.
    Leden, Ido
    Sektionen för reumatologi, Medicinska kliniken Centralsjukhuset, Kristianstad.
    Increased serum uric acid - a marker of non-gouty widespread pain?: a study of female patients with inflammatory and non-inflammatory pain2006In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, Vol. 35, no 4, 261-267 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the relationship between reported chronic pain and the level of serum urate (SU) among women with various diagnoses of the musculoskeletal system. METHODS: Consecutive female patients (aged 20-70 years, n = 124), at rheumatology and rehabilitation practices, with chronic musculoskeletal pain of different origins were followed for 1 year after an initial survey of pain, lifestyle, quality of life, and disability. Repeated blood samples (including urate, creatinine, cholesterol, and glucose) were analysed. Multiple regression analysis was performed to explain initial variations in SU level in relation to pain and confounding factors. RESULTS: The level of SU was increased among individuals with widespread pain (>5 locations) independent of underlying diagnoses compared to those with fewer pain sites (270.5 vs. 241.2 micromol/L). Serum creatinine, body mass index (BMI), the number of pain locations, and sleep disturbances independently contributed to the SU level and explained 43% of the variation in SU. Individual variation in SU during 4 months was low. CONCLUSIONS: Epidemiological data on the relationship between the extent of body pain and SU were confirmed in a clinical setting. Besides known factors such as impaired renal function and obesity, widespread pain and sleep disturbances were related to an increase in SU. Medication and alcohol intake could not explain the findings. Longitudinal studies are necessary to elucidate whether the level of SU has any implications for the prognosis of chronic pain.

  • 27.
    Andersson, Ingemar
    Kristianstad University, School of Health and Society.
    Långvarig smärta - en introduktion2010In: Smärta och smärtbehandling / [ed] Mads Werner, Ido Leden, Stockholm: Liber , 2010, 2, 387-400 p.Chapter in book (Other academic)
  • 28.
    Andersson, Ingemar
    Kristianstad University, School of Health and Society.
    Rehabilitering vid långvarig smärta2010In: Smärta och smärtbehandling / [ed] Mads Werner, Ido Leden, Stockholm: Liber , 2010, 2, 401-409 p.Chapter in book (Other academic)
  • 29.
    Andersson, Ingemar
    et al.
    Kristianstad University, Department of Health Sciences.
    Leden, Ido
    of Medicine, Division of Rheumatology, Kristianstad Central Hospital.
    Comment on: Glucose regulation and chronic pain at multiple sites.2009In: Rheumatology (Oxford, England), ISSN 1462-0332, Vol. 48, no 3, 324- p.Article in journal (Other academic)
  • 30.
    Andersson, Sofia E. M.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden..
    Eneljung, Tove
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden..
    Tengvall, Sara
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden..
    Jirholt, Pernilla
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden..
    Stern, Anna
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden..
    Henningsson, Louise
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden..
    Liang, Bibo
    Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Solna, Sweden.;Southern Med Univ, Guangzhou, Guangdong, Peoples R China..
    Thorarinsdottir, Katrin
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden..
    Kihlberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Holmdahl, Rikard
    Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Solna, Sweden.;Southern Med Univ, Guangzhou, Guangdong, Peoples R China..
    Martensson, Inga-Lill
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden..
    Gustafsson, Kenth
    UCL, Inst Child Hlth, Mol Immunol Unit, London, England..
    Gjertsson, Inger
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Box 480, SE-40530 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden..
    Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis2016In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 18, 140Article in journal (Refereed)
    Abstract [en]

    Background: The mechanisms underlying tolerance induction and maintenance in autoimmune arthritis remain elusive. In a mouse model of rheumatoid arthritis, collagen type II (CII)-induced arthritis, we explore the contribution of B cells to antigen-specific tolerance. Methods: To generate expression of the CII-peptide specifically on B-cell major histocompatibility complex type II, lentiviral-based gene therapy including a B-cell-specific Igk promoter was used. Results: Presentation of the CII-peptide on B cells significantly reduced the frequency and severity of arthritis as well as the serum levels of CII -specific IgG antibodies. Further, both frequency and suppressive function of regulatory T cells were increased in tolerized mice. Adoptive transfer of regulatory T cells from tolerized mice to naive mice ameliorated the development of CII-induced arthritis. Conclusion: Our data suggest that endogenous presentation of the CII-peptide on B cells is one of the key contributors to arthritis tolerance induction and maintenance.

  • 31. Apel, Maria
    et al.
    Uebe, Steffen
    Bowes, John
    Giardina, Emiliano
    Korendowych, Eleanor
    Juneblad, Kristina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Pasutto, Francesca
    Ekici, Arif B.
    McManus, Ross
    Ho, Pauline
    Bruce, Ian N.
    Ryan, Anthony W.
    Behrens, Frank
    Boehm, Beate
    Traupe, Heiko
    Lohmann, Joerg
    Gieger, Christian
    Wichmann, Heinz-Erich
    Padyukov, Leonid
    FitzGerald, Oliver
    Alenius, Gerd-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    McHugh, Neil J.
    Novelli, Giuseppe
    Burkhardt, Harald
    Barton, Anne
    Reis, Andre
    Hueffmeier, Ulrike
    Variants in RUNX3 Contribute to Susceptibility to Psoriatic Arthritis, Exhibiting Further Common Ground With Ankylosing Spondylitis2013In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, no 5, 1224-1231 p.Article in journal (Refereed)
    Abstract [en]

    Objective Psoriatic arthritis (PsA) is a common inflammatory joint disease distinct from other chronic arthritides and frequently accompanied by psoriasis vulgaris. In a first genome-wide association study (GWAS), we were able to identify several genetic risk factors. However, even combined with previously identified factors, the genetic contribution to disease was not fully explained. Therefore, we undertook this study to investigate further 17 loci from our GWAS that did not reach genome-wide significance levels of association in the initial analysis. Methods Twenty-one of 22 single-nucleotide polymorphisms were successfully genotyped in independent cohorts of 1,398 PsA patients and 6,389 controls and in a group of 964 German patients with psoriasis vulgaris. Results Association with a RUNX3 variant, rs4649038, was replicated in independent patients and controls and resulted in a combined P value of 1.40 x 108 by Cochran-Mantel-Haenszel test and an odds ratio (OR) of 1.24 (95% confidence interval [95% CI] 1.151.33). Further analyses based on linkage disequilibrium (LD) at RUNX3 refined the most significant association to an LD block located in the first intron of one isoform. Weaker evidence for association was detected in German patients with psoriasis vulgaris (P = 5.89 x 102; OR 1.13 [95% CI 1.001.28]), indicating a role in the skin manifestations of psoriasis. Conclusion Our analyses identified variants in RUNX3 as susceptibility factors for PsA. RUNX3 has already been implicated in susceptibility to ankylosing spondylitis, another spondyloarthritis, although its risk allele is independent from the one for PsA. RUNX-3 is involved in CD8+ T lymphocyte differentiation and is therefore a good candidate for involvement in PsA and psoriasis vulgaris as T cellmediated diseases.

  • 32.
    Areskoug Josefsson, Kristina
    Jönköping University, School of Health and Welfare, The Jönköping Academy for Improvement of Health and Welfare. Jönköping University, School of Health and Welfare, HHJ. IMPROVE (Improvement, innovation, and leadership in health and welfare).
    Sexual health in rheumatoid arthritis - The role of the physiotherapist to enhance sexual health2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, no Suppl. 2, 46-46 p.Article in journal (Refereed)
    Abstract [en]

    Sexual health is often negatively affected by rheumatoid arthritis (RA), but rarely discussed between patients and health care professionals. Experienced reasons for decreased sexual health vary among patients, but pain, stiffness, reduced mobility, fatigue and negative feelings towards one’s own body are common factors. In addition to negative effects experienced to be due to RA, there are also negative influences on sexual health by other factors, such as insufficient physical activity, low self-esteem, depression and stressful influences in life. Physiotherapy is a common intervention for patients with RA and patients have reported improved sexual health due to physiotherapy. Regular physiotherapy interventions for patients with RA often include coaching towards increasing physical activity levels, hydrotherapy, pain reductive treatment and mobility exercises, both individually and in groups. The physiotherapy interventions leading to improved sexual health (according to patients with RA) has been regular interventions for patients with RA and not specifically aimed at enhancing sexual health. The patients do seldom describe that the physiotherapist has informed them of how physiotherapy might enhance sexual health, but they have themselves experienced how physiotherapy has improved their sexual life. Patients describe that they experience joy, increased self-esteem and a more positive approach to their body, when participating in physiotherapy and that this positive feeling is affecting their life, including their sexual life. They also describe how increased physical capacity reduces fatigue and increases their capacity to engage in valued life activities, including sexual activities. The way that the physiotherapist can further enhance sexual health, is by informing the patient of how sexual health is linked to experienced symptoms of RA and how physiotherapy interventions, for example increasing physical activity, can enhance also sexual health

  • 33. Arkema, E.
    et al.
    Jonsen, A.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sjowall, C.
    Svenungsson, E.
    Simard, J. F.
    Utility of Swedish Register Data in Classifying Systemic Lupus2014In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, 444-444 p.Article in journal (Other academic)
  • 34. Arkema, Elizabeth V
    et al.
    Feltelius, Nils
    Olsson, Tomas
    Askling, Johan
    No association between rheumatoid arthritis, amyotrophic lateral sclerosis, and tumour necrosis factor inhibitor treatment.2014In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, no 11Article in journal (Refereed)
  • 35. Arkema, Elizabeth V
    et al.
    Jönsen, Andreas
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Svenungsson, Elisabet
    Sjöwall, Christopher
    Simard, Julia F
    Case definitions in Swedish register data to identify systemic lupus erythematosus2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 1, e007769Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To develop and investigate the utility of several different case definitions for systemic lupus erythematosus (SLE) using national register data in Sweden.

    METHODS: The reference standard consisted of clinically confirmed SLE cases pooled from four major clinical centres in Sweden (n=929), and a sample of non-SLE comparators randomly selected from the National Population Register (n=24 267). Demographics, comorbidities, prescriptions and autoimmune disease family history were obtained from multiple registers and linked to the reference standard. We first used previously published SLE definitions to create algorithms for SLE. We also used modern data mining techniques (penalised least absolute shrinkage and selection operator logistic regression, elastic net regression and classification trees) to objectively create data-driven case definitions. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the case definitions identified.

    RESULTS: Defining SLE by using only hospitalisation data resulted in the lowest sensitivity (0.79). When SLE codes from the outpatient register were included, sensitivity and PPV increased (PPV between 0.97 and 0.98, sensitivity between 0.97 and 0.99). Addition of medication information did not greatly improve the algorithm's performance. The application of data mining methods did not yield different case definitions.

    CONCLUSIONS: The use of SLE International Classification of Diseases (ICD) codes in outpatient clinics increased the accuracy for identifying individuals with SLE using Swedish registry data. This study implies that it is possible to use ICD codes from national registers to create a cohort of individuals with SLE.

  • 36.
    Arkema, Elizabeth V
    et al.
    1Clinical Epidemiology Unit, Department of Medicine, Solna Karolinska Institute, Stockholm.
    Jönsen, Andreas
    Department of Clinical Sciences, Lund University, Lund.
    Rönnblom, Lars
    Department of Medical Sciences, Science for Life Laboratories, Uppsala University, Uppsala.
    Svenungsson, Elisabet
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Simard, Julia F
    Clinical Epidemiology Unit, Department of Medicine, Solna Karolinska Institute, Stockholm.
    Case definitions in Swedish register data to identify systemic lupus erythematosus2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 1Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To develop and investigate the utility of several different case definitions for systemic lupus erythematosus (SLE) using national register data in Sweden.

    METHODS: The reference standard consisted of clinically confirmed SLE cases pooled from four major clinical centres in Sweden (n=929), and a sample of non-SLE comparators randomly selected from the National Population Register (n=24 267). Demographics, comorbidities, prescriptions and autoimmune disease family history were obtained from multiple registers and linked to the reference standard. We first used previously published SLE definitions to create algorithms for SLE. We also used modern data mining techniques (penalised least absolute shrinkage and selection operator logistic regression, elastic net regression and classification trees) to objectively create data-driven case definitions. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the case definitions identified.

    RESULTS: Defining SLE by using only hospitalisation data resulted in the lowest sensitivity (0.79). When SLE codes from the outpatient register were included, sensitivity and PPV increased (PPV between 0.97 and 0.98, sensitivity between 0.97 and 0.99). Addition of medication information did not greatly improve the algorithm's performance. The application of data mining methods did not yield different case definitions.

    CONCLUSIONS: The use of SLE International Classification of Diseases (ICD) codes in outpatient clinics increased the accuracy for identifying individuals with SLE using Swedish registry data. This study implies that it is possible to use ICD codes from national registers to create a cohort of individuals with SLE.

  • 37.
    Arkema, Elizabeth V
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Palmsten, Kristin
    University of California, San Diego, USA.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Svenungsson, Elisabet
    Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Salmon, Jane E
    Weill Cornell Medical College, New York, New York.
    Simard, Julia F
    Stanford School of Medicine, Stanford, California, USA ;Karolinska Institute, Stockholm, Sweden.
    What to Expect When Expecting With Systemic Lupus Erythematosus (SLE): A Population-Based Study of Maternal and Fetal Outcomes in SLE and Pre-SLE.2016In: Arthritis care & research, ISSN 2151-464X, E-ISSN 2151-4658, Vol. 68, no 7Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess maternal and fetal outcomes associated with subclinical (pre-systemic lupus erythematosus [SLE] and SLE presenting up to 5 years postpartum) and prevalent maternal SLE during pregnancy compared with the general population.

    METHODS: This prospective cohort study used population-based Swedish registers to identify 13,598 women with first singleton pregnancies registered in the Medical Birth Register (551 prevalent SLE, 65 pre-SLE within 0-2 years, 133 pre-SLE within 2-5 years, and 12,847 general population). SLE was defined as ≥2 SLE-coded discharge diagnoses in the patient register with ≥1 diagnosis from a specialist. Unadjusted risks of adverse pregnancy or birth outcomes were calculated by SLE status, and Cochran-Armitage tests evaluated trend across exposure groups.

    RESULTS: Maternal outcomes such as preeclampsia, hypothyroidism, stroke, and infection were more common among women with SLE. Sixteen percent of prevalent-SLE pregnancies were diagnosed with preeclampsia compared with 5% of those from the general population. Among the pre-SLE women, preeclampsia was found in 26% of those with SLE within 2 years postpartum and 13% in those with SLE within 2-5 years postpartum. Similarly, infant outcomes, such as preterm birth, infection, and mortality, were worse among those born to mothers with prevalent SLE and pre-SLE during pregnancy. The test for trend was significant for most outcomes.

    CONCLUSION: Our data demonstrate that adverse maternal and fetal outcomes are more common in SLE pregnancies. Furthermore, these unfavorable outcomes are observed in pregnancies occurring prior to the diagnosis of SLE. Thus, the underlying immunologic profile of SLE and alterations preceding clinical SLE may contribute to these pregnancy complications.

  • 38. Arkema, Elizabeth V
    et al.
    van Vollenhoven, Ronald F
    Askling, Johan
    Incidence of progressive multifocal leukoencephalopathy in patients with rheumatoid arthritis: a national population-based study2012In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, no 11, 1865-1867 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cases of progressive multifocal leukoencephalopathy (PML), a rare but serious disease, have been reported in patients with rheumatoid arthritis (RA) in association with biological therapy, but little is known about the incidence of PML in patients with RA in the absence of treatment exposure.

    OBJECTIVE: To estimate the incidence rate of PML in patients with RA compared with the general population, with and without exposure to biological agents.

    METHODS: Patients with adult onset RA, exposure to biological agents and a diagnosis of PML from 1999 through 2009 were identified from national registries and linked using each Swedish resident's unique personal identification number. General population comparators matched on age, sex and county were also identified. Crude and age- and sex-standardised incidence rates (cases per 100 000 person-years) were calculated with 95% CI.

    RESULTS: 66 278 patients with RA and 286 949 general population comparators were included in the study. The incidence rate of PML in the overall RA population was 1.0 (95% CI 0.3 to 2.5) compared with 0.3 (95% CI 0.1 to 0.6) in the general population. The difference in incidence rate was 0.7 (95% CI -0.3 to 17). Among all patients exposed to biological agents, only one patient was diagnosed with PML.

    CONCLUSION: Data from this national population-based cohort study suggest that patients with RA may have an increased rate of PML compared with the general population.

  • 39.
    Arvonen, Miika
    et al.
    Kuopio Univ Hosp, Dept Pediat, Kuopio, Finland.;Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland..
    Berntson, Lillemor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Pokka, Tytti
    Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland.;Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland..
    Karttunen, Tuomo J.
    Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, Canc & Translat Med Res Unit, Oulu, Finland.;Oulu Univ Hosp, Dept Pathol, Oulu, Finland..
    Vahasalo, Paula
    Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland.;Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland..
    Stoll, Matthew L.
    Univ Alabama Birmingham, Dept Pediat, CPP N 210 M,1600 7th Ave South, Birmingham, AL 35233 USA..
    Gut microbiota-host interactions and juvenile idiopathic arthritis2016In: Pediatric Rheumatology, ISSN 1546-0096, E-ISSN 1546-0096, Vol. 14, 44Article, review/survey (Refereed)
    Abstract [en]

    Background: Juvenile idiopathic arthritis is the most common form of chronic arthritis in children. There is mounting evidence that the microbiota may influence the disease. Main body: Recent observations in several systemic inflammatory diseases including JIA have indicated that abnormalities in the contents of the microbiota may be factors in disease pathogenesis, while other studies in turn have shown that environmental factors impacting the composition of the microbiota, such as delivery mode and early exposure to antibiotics, affect the risk of chronic inflammatory diseases including JIA. Microbial alterations may predispose to JIA through a variety of mechanisms, including impaired immunologic development, alterations in the balances of pro- versus anti-inflammatory bacteria, and low-grade mucosal inflammation. Additional confirmatory studies of microbiota aberrations and their risk factors are needed, as well as additional mechanistic studies linking these alterations to the disease itself. Conclusions: The microbiota may influence the risk of JIA and other systemic inflammatory conditions through a variety of mechanisms. Additional research is required to improve our understanding of the links between the microbiota and arthritis, and the treatment implications thereof.

  • 40.
    Askling, J
    et al.
    Karolinska University Hospital, Stockholm, Sweden.
    Baecklund, E
    Uppsala University Hospital, Uppsala, Sweden.
    Granath, F
    Karolinska University Hospital, Stockholm, Sweden.
    Geborek, P
    Lund University Hospital, Lund, Sweden.
    Fored, M
    Karolinska University Hospital, Stockholm, Sweden.
    Backlin, C
    Uppsala University, Uppsala, Sweden.
    Bertilsson, L
    Sahlgrens University Hospital, Gothenburg, Sweden.
    Cöster, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Jacobsson, L T
    Malmö University Hospital, Malmö, Sweden.
    Lindblad, S
    Karolinska University Hospital, Stockholm, Sweden.
    Lysholm, J
    Falu County Hospital, Falun, Sweden.
    Rantapaa-Dahlqvist, S
    Umeå University Hospital, Umeå, Sweden.
    Saxne, T
    University of Lund Hospital, Lund, Sweden.
    van Vollenhoven, R
    Karolinska University Hospital, Stockholm, Sweden.
    Klareskog, L
    Karolinska University Hospital, Stockholm, Sweden.
    Feltelius, N
    Medical Products Agency, Uppsala, Sweden.
    Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register2009In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 68, no 5, 648-653 p.Article in journal (Refereed)
    Abstract [en]

    Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis ( RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.

    Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 ( n = 6604) were identified. A general population comparator ( n = 471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.

    Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients ( 336 lymphomas during 365 026 person-years) and 2.72 ( 95% CI 1.82 to 4.08) versus the general population comparator ( 1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.

    Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.

  • 41. Askling, J
    et al.
    Fored, C M
    Brandt, L
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Bertilsson, L
    Feltelius, N
    Medical Products Agency, Uppsala, Sweden .
    Cöster, L
    Geborek, P
    Jacobsson, L T
    Lindblad, S
    Lysholm, J
    Rantapää-Dahlqvist, S
    Saxne, T
    Klareskog, L
    Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists2005In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, no 10, 1421-1426 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s.

    OBJECTIVE:

    To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials.

    METHODS:

    A population based study of three RA cohorts (one prevalent, admitted to hospital 1990-2003 (n = 53,067), one incident, diagnosed 1995-2003 (n = 3703), and one treated with TNF antagonists 1999-2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003.

    RESULTS:

    With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20-50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (-20%) and colorectal cancer (-25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA.

    CONCLUSION:

    The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.

  • 42. Askling, J
    et al.
    Klareskog, L
    Hjalgrim, H
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Björkholm, M
    Ekbom, A
    Do steroids increase lymphoma risk? A case-control study of lymphoma risk in polymyalgia rheumatica/giant cell arteritis2005In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, no 12, 1765-1768 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Recent studies indicate increased risks of malignant lymphomas among individuals treated with corticosteroids, but have not taken into account the underlying reasons for steroid use, so the increased risks might be attributable to the underlying disease or concomitant treatments other than steroids. Polymyalgia rheumatica (PMR) and temporal arteritis (giant cell arteritis, GCA) are common inflammatory conditions treated with steroids as single immunosuppressive therapy, but data on lymphoma risk in GCA/PMR are limited.

    OBJECTIVE:

    To assess the risk of lymphoma associated with steroid treatment of GCA/PMR.

    METHODS:

    The association between GCA/PMR and malignant lymphomas (overall, and separately for non-Hodgkin lymphoma, Hodgkin lymphoma, and chronic lymphatic leukaemia) was examined in a nationwide, population based, case-control study of 42,676 lymphoma cases and 78,487 matched population controls, using prospectively recorded data on lymphomas from the Swedish cancer register 1964-2000 and data on pre-lymphoma hospital admissions for GCA/PMR from the Swedish inpatient register 1964-2000. Odds ratios (OR) associated with a pre-lymphoma hospital admission for GCA/PMR were calculated using conditional logistic regression.

    RESULTS:

    153 lymphoma cases and 345 population controls had a history of GCA/PMR, resulting in an overall OR for malignant lymphomas of 0.81 (95% confidence interval, 0.67 to 0.98). The OR varied little with lymphoma type, sex, age, and calendar period. The OR for GCA was 0.67 (0.48 to 0.98) and for PMR, 0.83 (0.67 to 1.04).

    CONCLUSIONS:

    Treated GCA is not associated with increased lymphoma risks, which suggests that even at considerable cumulative doses, steroids may not appreciably increase lymphoma risk.

  • 43.
    Askling, Johan
    et al.
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    van Vollenhoven, Ronald F
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Granath, Fredrik
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Raaschou, Pauline
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Fored, C Michael
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Baecklund, Eva
    Uppsala University Hospital, Uppsala, Sweden.
    Dackhammar, Christina
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Feltelius, Nils
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Cöster, Lars
    Linköping University Hospital, Linköping, Sweden.
    Geborek, Pierre
    Lund University Hospital, Lund, Sweden.
    Jacobsson, Lennart T
    Malmö University Hospital, Malmö, Sweden.
    Lindblad, Staffan
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Saxne, Tore
    Lund University Hospital, Lund, Sweden.
    Klareskog, Lars
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor α therapies: does the risk change with the time since start of treatment?2009In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, no 11, 3180-3189 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions. METHODS: By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received. RESULTS: During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed. CONCLUSION: During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.

  • 44.
    Bala, Sidona-Valentina
    et al.
    Department of Health Sciences, Lund University, Lund, Sweden.
    Samuelson, Karin
    Department of Health Sciences, Lund University, Lund, Sweden .
    Hagell, Peter
    The PRO-CARE Group, School of Health and Society, Kristianstad University, Kristianstad, Sweden.
    Fridlund, Bengt
    Jönköping University, School of Health and Welfare, HHJ. ADULT. Department of Health Sciences, Lund University, Lund, Sweden .
    Forslind, Kristina
    Section of Rheumatology, Department of Medicine, Helsingborg Hospital, Helsingborg, Sweden.
    Svensson, Björn
    Section of Rheumatology at the Institution of Clinical Science, Lund University, Lund, Sweden.
    Thomé, Bibbi
    Department of Health Sciences, Lund University, Lund, Sweden .
    Living with persistent rheumatoid arthritis: A BARFOT study2017In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702Article in journal (Refereed)
    Abstract [en]

    Aim and objective: To describe and understand the meaning of living with persistent rheumatoid arthritis.

    Background: A considerable number of patients with rheumatoid arthritis live with an ongoing active and symptomatic illness despite access to potent antirheumatic treatment. There is, however, a lack of knowledge about the meaning of living with this severe long-term illness, defined as persistent rheumatoid arthritis.

    Design: A descriptive design based on a hermeneutic phenomenological method was used.

    Methods: Ten adults with persistent rheumatoid arthritis and at least five years disease duration were interviewed. The interviews were analysed according to van Manen's method.

    Results: Living with persistent rheumatoid arthritis revealed four overall themes: an existence dominated by painful symptoms and treatment, radical changes and limitations in one's life, a continual struggle to cope with one's life and to master the illness, and a dependency on those who are close by and the world around. The lifeworld was affected to a varying extent and in various ways by the illness but also by the dependence on its treatment and care that was not experienced as sufficiently meeting needs in terms of security, access to and coordination of care as well as team and rehabilitation services.

    Conclusions: Persistent rheumatoid arthritis and its treatment entail a radical effect on the person's life and quality of life. Current ordinary rheumatology care does not seem to meet the individual needs of the person with persistent rheumatoid arthritis in an optimal way.

    Relevance to clinical practice: A greater knowledge about and understanding of the person who lives with persistent rheumatoid arthritis is important for facilitating the development of care and the relief of suffering. A holistic alternative to conventional clinical practice, such as person-centred care, could be tested as an innovative model of care. Our findings might serve as material for educational and counselling purposes for healthcare professionals. 

  • 45. Balboni, Imelda
    et al.
    Niewold, Timothy B
    Morgan, Gabrielle
    Limb, Cindy
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Utz, Paul J
    Pachman, Lauren M
    Brief Report: Interferon-α Induction and Detection of Anti-Ro, Anti-La, Anti-Sm, and Anti-RNP Autoantibodies by Autoantigen Microarray Analysis in Juvenile Dermatomyositis2013In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, no 9, 2424-2429 p.Article in journal (Refereed)
    Abstract [en]

    Objective:

    To evaluate serum interferon- (IFN) activity in the context of autoantibody profiles in patients with juvenile dermatomyositis (JDM). 

    Methods:

    Sera from 36 patients with JDM were analyzed. Autoantibody profiles were determined by probing microarrays, which were fabricated with approximate to 80 distinct autoantigens, with serum and a Cy3-conjugated secondary antibody. Arrays were scanned and analyzed to determine antigen reactivity. Serum IFN activity was measured using a functional reporter cell assay. Sera were assayed alone or in combination with cellular material released from necrotic U937 cells to stimulate peripheral blood mononuclear cells from healthy donors in vitro, and IFN production in culture was measured by a dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). 

    Results:

    Reactivity against at least 1 of 41 autoantigens on the microarray, including Ro 52, Ro 60, La, Sm, and RNP, was observed in 75% of the serum samples from patients with JDM. IFN activity was detected in 7 samples by reporter cell assay. The reporter cell assay showed a significant association of reactivity against Ro, La, Sm, and proliferating cell nuclear antigen with serum IFN activity (P = 0.005). Significance Analysis of Microarrays (SAM) identified increased reactivity against Sm, RNP, Ro 52, U1-C, and Mi-2 in these sera. Sixteen samples induced IFN production as measured by DELFIA, and there was a significant association of reactivity against Ro, La, Sm, and RNP with the induction of IFN by serum and necrotic cell material (P = 0.034). SAM identified increased reactivity against Ro 60 in these sera. 

    Conclusion:

    These data support the hypothesis that nucleic acid-associated autoantibodies, including the Ro/La and Sm/RNP complexes, may stimulate the production of active IFN in children with JDM.

  • 46.
    Barbe, MF
    et al.
    Department of Anatomy and Cell biology, Temple University, Philadelphia, USA.
    Xin, DL
    Department of Surgery, University of Pennsylvania, USA.
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Elliott, ME
    Department of Neurosurgery, Thomas Jefferson University, USA.
    Barr-Gillespie, A
    College of Health Professions, Pacific University, USA.
    Sickness behaviors (reduced social interaction and pain behaviors) are linked to inflammatory mechanisms in a rat model of work-related musculoskeletal disorders2016In: Proceedings of the Human Factors and Ergonomics Society Annual Meeting, ISSN 1541-9312, Vol. 60, no 1, 975-979 p.Article in journal (Refereed)
    Abstract [en]

    We sought to determine if sickness behaviors (decreased social interaction and pain) are induced in a rat model of work-related overuse and effectiveness of anti-inflammatory treatments. Rats first trained to learn a high force reaching task (15 min/week day for 6 wks), with subsets treated prophylactically with ibuprofen or anti-TNFalpha. Others performed a high repetition high force (HRHF) task for 6 or 12 weeks (2 hrs/day, 3 days/wk) untreated, or with ibuprofen, anti-TNFalpha or rest treatments beginning task week 5. Untreated HRHF rats had increased IL-1beta, IL-6 and TNFalpha in serum and brain, increased Substance P in spinal cord, decreased social interaction and increased forepaw allodynia. Secondary antiinflammatory treatments attenuated social interaction and brain changes, but not allodynia or spinal cord changes; rest provided partial attenuation. Prophylactic treatments prevented all changes. Thus, inflammatory mechanisms mediate the development of sickness behaviors induced by work-related overuse, but not maintenance of allodynia.

  • 47.
    Bengtsson, A. A.
    et al.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Systemic lupus erythematosus: still a challenge for physicians2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 1, 52-64 p.Article, review/survey (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE) has a complex clinical picture, and a number of defects in the immune system have been described in patients with the disease. Most organs can be involved in SLE, and in addition to the typical major organ manifestations (e.g. from kidneys and the central nervous system), early cardiovascular disease is a major determinant of prognosis. Several important findings during the last decade have increased the understanding of the mechanisms behind the disease characteristics and the underlying autoimmune process. Amongst, these are defects in the handling of apoptotic cells, increased expression of type I interferon-regulated genes and activation of autoreactive B cells, with both the type I interferon system and the B lymphocyte stimulator (BLyS) having key roles. In addition, a large number of genes have been identified that contribute to these abnormalities. It has also become clear that certain SLE risk genes are associated with some organ manifestations, such as STAT4 with nephritis and IRF8 with myocardial infarction. Furthermore, environmental factors that can induce SLE or trigger a disease flare have been identified. As a consequence of this increased knowledge, new treatments for SLE have been developed. The most recently approved drug for SLE is belimumab, which blocks BLyS, and several new therapies and therapeutic strategies are in the pipeline for clinical application.

  • 48. Bengtsson, Anders A
    et al.
    Sturfelt, Gunnar
    Lood, Christian
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    van Vollenhoven, Ronald F
    Axelsson, Bengt
    Sparre, Birgitta
    Tuvesson, Helén
    Wallén Öhman, Marie
    Leanderson, Tomas
    Pharmacokinetics, tolerability, and preliminary efficacy of ABR-215757, a new quinoline-3-carboxamide derivative, in murine and human SLE2012In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, no 5, 1579-1588 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the efficacy of ABR-215757, a new immunomodulatory small molecule in a murine SLE model, to evaluate the pharmacokinetics and tolerability in SLE patients at doses predicted to be efficacious and safe, and to determine the maximum tolerated dose (MTD).

    METHODS: The efficacy of ABR-215757 was studied in lupus prone MRLlpr/lpr mice and compared with established SLE treatments. Dose response data of ABR-215757 were together with pharmacokinetic data used to calculate effective and safe clinical doses. The pharmacokinetics and tolerance of ABR-215757 were evaluated in a Phase Ib double-blind, placebo controlled, dose-escalation study where cohorts of SLE patients received daily oral treatment for 12 weeks.

    RESULTS: Disease inhibition in MRLlpr/lpr mice, comparable to that of prednisolone and mycophenolate mofetil, was obtained with ABR-215757. Prominent effects on disease manifestations, serological markers and a steroid sparing effect were seen for ABR-215757. The pharmacokinetic properties in SLE patients were linear and well suitable for once daily oral treatment. The majority of the adverse events (AEs) were mild or moderate and transient. The most frequent AEs were arthralgia and myalgia, reported at the highest (4.5 and 6 mg/day) dose levels. At 4.5 mg and higher some AEs of severe intensity and serious adverse events (SAEs) were reported.

    CONCLUSION: ABR-215757 effectively inhibited disease and had a steroid sparing effect in experimental lupus. Clinical doses up to 3 mg/day, dose levels predicted from pre-clinical studies to be efficacious and safe, were well tolerated in the SLE patients. The MTD was concluded to be 4.5 mg/day.

  • 49.
    Bengtsson, C.
    et al.
    Department of Rheumatology, Östersund Hospital, Sweden .
    Bengtsson, A. A.
    Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Costenbader, K. H.
    Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA .
    Jönsen, A.
    2Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Sturfelt, G.
    Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Nived, O.
    Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Systemic lupus erythematosus and cardiac risk factors: medical record documentation and patient adherence2011In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 20, no 10, 1057-1062 p.Article in journal (Refereed)
    Abstract [en]

    This study explores patients' knowledge of cardiac risk factors (CRFs), analyses how information and advice about CRFs are documented in clinical practice, and assesses patient adherence to received instructions to decrease CRFs. Systemic lupus erythematosus (SLE) patients with >= 4 ACR criteria participated through completing a validated cardiovascular health questionnaire (CHQ). Kappa statistics were used to compare medical records with the self-reported CHQ (agreement) and to evaluate adherence. Two hundred and eleven (72%) of the known patients with SLE participated. The mean age of the patients was 55 years. More than 70% of the SLE patients considered hypertension, obesity, smoking and hypercholesterolaemia to be very important CRFs. The agreement between medical record documentation and patients' reports was moderate for hypertension, overweight and hypercholesterolaemia (kappa 0.42-0.60) but substantial for diabetes (kappa 0.66). Patients' self-reported adherence to advice they had received regarding medication was substantial to perfect (kappa 0.65-1.0). For lifestyle changes in patients with hypertension and overweight, adherence was only fair to moderate (kappa 0.13-0.47). Swedish SLE patients' awareness of traditional CRFs was good in this study. However, the agreement between patients' self-reports and medical record documentation of CRF profiles, and patients' adherence to medical advice to CRF profiles, could be improved. Lupus (2011) 20, 1057-1062.

  • 50. Bengtsson, C
    et al.
    Öhman, Marie-Louise
    Nived, O
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Cardiovascular event in Systemic Lupus Erythematosus in northern Sweden: incidence and predictors in a 7-year follow up study2012In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 21, no 4, 452-459 p.Article in journal (Refereed)
    Abstract [en]

    Introduction. An increased rate of cardiovascular disease (CVD) has been suggested in patients with systemic lupus erythematosus (SLE). The risk for myocardial infarction (MI), coronary artery disease and stroke has been reported as particularly prevalent in younger females compared with the reference population. This study was performed to analyse the standard incidence ratio (SIR) of and predictors for cardiovascular events (CVEs) in patients with SLE from northern Sweden, with a fairly homogenous population.

    Methods. In 2000 all prevalent patients with SLE (≥4 American College of Rheumatology [ACR] criteria; n = 277) from the four northern-most counties of Sweden were assessed with clinical and laboratory analyses. Seven years follow-up data concerning MI and stroke were extracted from the national registers of hospitalization and death in Sweden. The incidence ratio among the patients was compared with that for the general population from the same catchment area using data from the same register and Statistics Sweden. To identify time to event and CVE predictors, two matched controls for each patient were used and disease related variables as CVD predictors.

    Results. The SIR for a CVE was 1.27 (95% CI 0.82-1.87) and for females separately aged 40-49 years was 8.00 (95% CI 1.65-23.38). The overall SIR for MI was 2.31 (95% CI 1.34-3.7), for females overall was 1.75 (95% CI 0.84-3.22) and for females aged between 40 and 49 years was 8.7 (95% CI 1.1-31.4). The time to an event was significantly shorter among SLE patients (p < 0.001) and was predicted by hypertension adjusted for smoking and disease. High SLEDAI and anti-cardiolipin IgG antibodies predicted an event in Cox proportional hazards regression models adjusted for age and previous MI. Diabetes, smoking ever and sex did not affect the prediction models.

    Conclusion. The risk of a CVE, or MI, was eight- or nine-fold greater among middle-aged female SLE patients. Time to event was significantly shorter and CVE was associated with SLE-related factors including hypertension and age.

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