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  • 1. 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, p. 17-28Article, 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.

  • 2. Agca, Rabia
    et al.
    Heslinga, Sjoerd C.
    Rollefstad, S.
    Heslinga, S.
    Södergren, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Semb, A. G.
    Kitas, George D.
    Sattar, Naveed
    Nurmohamed, Michael T.
    Response to: "Influence of changes in cholesterol levels and disease activity on the 10-year cardiovascular risk estimated with different algorithms in rheumatoid arthritis patients" by Fornaro et al2020In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 79, no 9, article id e105Article in journal (Refereed)
  • 3. Aglago, Elom K.
    et al.
    Rinaldi, Sabina
    Freisling, Heinz
    Jiao, Li
    Hughes, David J.
    Fedirko, Veronika
    Schalkwijk, Casper G.
    Weiderpass, Elisabete
    Dahm, Christina C.
    Overvad, Kim
    Eriksen, Anne Kirstine
    Kyrø, Cecilie
    Boutron-Ruault, Marie-Christine
    Rothwell, Joseph A.
    Severi, Gianluca
    Katzke, Verena
    Kühn, Tilman
    Schulze, Matthias B.
    Aleksandrova, Krasimira
    Masala, Giovanna
    Krogh, Vittorio
    Panico, Salvatore
    Tumino, Rosario
    Naccarati, Alessio
    Bueno-de-Mesquita, Bas
    van Gils, Carla H.
    Sandanger, Torkjel M.
    Gram, Inger T.
    Skeie, Guri
    Quirós, J. Ramón
    Jakszyn, Paula
    Sánchez, Maria-Jose
    Amiano, Pilar
    Huerta, José María
    Ardanaz, Eva
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Odontology.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Perez-Cornago, Aurora
    Mayén, Ana-Lucia
    Cordova, Reynalda
    Gunter, Marc J.
    Vineis, Paolo
    Cross, Amanda J.
    Riboli, Elio
    Jenab, Mazda
    Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort2021In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 30, no 1, p. 182-192Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.

    METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.

    RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).

    CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.

    IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.

  • 4. 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, p. 17-23Article 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.

  • 5.
    Ahlsved, Anton
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Betydelsen av synovit i fot för sjukdomsaktiviteten vidreumatoid artrit2023Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 6.
    Alaish, Ram
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundgren, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Safety of azathioprine and 6-mercaptopurine in patients with inflammatory bowel disease naive to thiopurine treatment2017In: International journal of clinical pharmacology and therapeutics, ISSN 0946-1965, Vol. 55, no 7, p. 594-600Article in journal (Refereed)
    Abstract [en]

    Objectives: To determine if 6-mercaptopurine (MP) is better tolerated than azathioprine (AZA) as the initial thiopurine treatment in patients suffering from inflammatory bowel disease (IBD). Switching patients with IBD from AZA to MP is advocated in patients intolerant to AZA. However, no study has determined if MP is more suited than AZA as a first-line treatment for patients who are naive to thiopurine treatment. Study: The tolerance of AZA and MP treatments in clinical practice was retrospectively evaluated from start to 12 months after initiating treatment in 113 patients with IBD who were all naive to thiopurines (82 patients treated with AZA and 31 patients with MP). Results: 65% of the patients treated with AZA and 61% of the patients treated with MP tolerated their treatment during 12 months (i.e., no group difference, p = 0.742). No difference in reported side effects between the two treatments was observed. The mean equivalent initial dose (0.92 vs. 0.61 mg/kg; p < 0.001) and the mean equivalent dose at 12 months (1.98 vs. 1.65 mg/kg; p = 0.014) was significantly higher in the MP group vs. the AZA group. The proportion of patients with.MCV = 7 at 12 months was numerically higher in the MP group than in the AZA group (53% vs. 31%; p = 0.090). Conclusions: In this retrospective observational study, no differences in tolerance or adherence between AZA and MP were observed in patients naive to thiopurines. However, MP treatment was at a higher equivalent thiopurine dose than AZA treatment, which tended to be associated with better treatment response.

  • 7.
    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, p. 760-760Article in journal (Refereed)
  • 8.
    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, p. 120-123Article 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.

  • 9.
    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, p. S150-S150, Meeting Abstract: 346Article in journal (Other academic)
  • 10.
    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, p. 357-362Article 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.

  • 11. 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, p. R15-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.

  • 12. 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, p. R153-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.

  • 13. 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, p. 265-Article in journal (Refereed)
  • 14.
    Anan, Intissar
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Bång, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Westermark, Per
    A case report of osteoarthritis associated with hereditary transthyretin amyloidosis ATTRV30M2019In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, p. 29-30Article in journal (Refereed)
  • 15. 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, p. S908-S908Article in journal (Refereed)
  • 16.
    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, p. 1085-1093Article 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.

  • 17.
    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, p. 1324-1332Article 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.

  • 18. Andersson, K.
    et al.
    Pullerits, R.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Dept Rheumatology and inflammation research, Inst Medicine, Göteborg university, Göteborg.
    Erlandsson, M.
    Silfversward, T.
    Bokarewa, M.
    Oestrogen dependent regulation of micro-rna in rheumatoid arthritis2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, p. 236-237Article in journal (Other academic)
  • 19. 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, p. 1224-1231Article 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.

  • 20. Askling, Johan
    et al.
    Baecklund, Eva
    Granath, Fredrik
    Geborek, Pierre
    Fored, Michael
    Backlin, Carin
    Bertilsson, Lennart
    Cöster, Lars
    Jacobsson, Lennart
    Lindblad, Staffan
    Lysholm, Jörgen
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Saxne, Tore
    van Vollenhoven, Ronald
    Klareskog, Lars
    Feltelius, Nils
    Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register2008In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 68, no 5, p. 648-653Article 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.

  • 21. Askling, Johan
    et al.
    Holmqvist, Marie
    Ljung, Lotta
    Umeå University. Karolinska Institutet, Stockholm, Sweden.
    Is Rheumatoid Arthritis a Mortal Disease?2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no 8, p. 1509-1511Article in journal (Refereed)
  • 22.
    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, p. 3180-3189Article 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.

  • 23.
    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, p. 975-979Article 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.

  • 24. Benatar, Michael
    et al.
    Wuu, Joanne
    Lombardi, Vittoria
    Jeromin, Andreas
    Bowser, Robert
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malaspina, Andrea
    Neurofilaments in pre-symptomatic ALS and the impact of genotype2019In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 20, no 7-8, p. 538-548Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate serum and cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy (pNfH), and to compare these to levels of neurofilament light (NfL), as biomarkers of pre-symptomatic ALS. Design. The study population includes 34 controls, 79 individuals at-risk for ALS, 22 ALS patients, and 14 phenoconverters. At-risk individuals are enrolled through Pre-Symptomatic Familial ALS (Pre-fALS), a longitudinal natural history and biomarker study of individuals who are carriers of any ALS-associated gene mutation, but who demonstrate no clinical evidence of disease at the time of enrollment. pNfH and NfL in serum and CSF were quantified using established enzyme-linked immunosorbent assays. Results. There is a longitudinal increase in serum pNfH in advance of the emergence of clinically manifest ALS. A similar pattern is observed for NfL, but with the absolute levels also frequently exceeding a normative threshold. Although CSF data are more sparse, similar patterns are observed for both neurofilaments, with absolute levels exceeding a normative threshold prior to phenoconversion. In serum, these changes are observed in the 6-12 months prior to disease among SOD1 A4V mutation carriers, and as far back as 2 and 3.5 years, respectively, in individuals with a FUS c.521del6 mutation and a C9ORF72 hexanucleotide repeat expansion. Conclusions. Serum and CSF pNfH increase prior to phenoconversion. In CSF, the temporal course of these changes is similar to NfL. In serum, however, pNfH is less sensitive to pre-symptomatic disease than NfL. The duration of pre-symptomatic disease, as defined by changes in neurofilaments, may vary depending on underlying genotype.

  • 25.
    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, p. 1057-1062Article 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.

  • 26.
    Bengtsson, C.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Wahlin, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Braune, A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Jonsson, E.
    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.
    Hydroxychloroquine improves the blood lipid profile in rheumatoid arthritis and systemic lupus erythematosus after four and eight weeks of treatment: a randomized interventional study2018In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, p. 29-29Article in journal (Other academic)
  • 27. 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, p. 452-459Article 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.

  • 28. Bengtsson, Christine
    et al.
    Öhman, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Prediction of cardiovascular event in systemic lupus erythematosus in northern Sweden: a 7-year follow up study2010In: Scandinavian Journal of Rheumatology. Supplement, ISSN 0301-3847, E-ISSN 1502-7740, Vol. 39, no Suppl.124, p. S28-Article in journal (Refereed)
  • 29. Bengtsson, K.
    et al.
    Askling, J.
    Lorentzon, M.
    Rosengren, B.
    Deminger, A.
    Klingberg, E.
    Jacobsson, L. T. H.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Higher risk of incident fracture in patients with ankylosing spondylitis compared to the general population2020In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 79, p. 745-746, article id FRI0310Article in journal (Other academic)
    Abstract [en]

    Background: Ankylosing spondylitis (AS) is characterized by pathologic new bone formation and bone loss. Vertebral fracture (VF) is a known complication of AS, whereas the risk of other major osteoporotic fractures (MOFs) is less studied.

    Objectives: To estimate incidence rates (IRs) of incident fractures (any, VF and other MOF (humerus, forearm and hip)) in patients with AS compared to controls from general population.

    Methods: This is a nationwide, register-based and observational cohort study including patients diagnosed with AS (n=11611, 65% men, mean age 48 years) identified in the National patient register (NPR) 2001 through 2015, and age- and sex-matched controls (n=58050) from the Swedish Population Register. The study period started 1 January 2007 or 3 months after the first AS diagnosis, whichever came later, and ended at the first occurrence of each fracture outcome (identified in the NPR), death, emigration or 31 December 2016. Patients and controls with any prior fracture in NPR within a 6-year period before start of the study period were not included. Any fracture (except skull and phalangeal fractures), VF and other MOF were identified in NPR according to pre-specified ICD codes. Each fracture outcome was analysed separately. Poisson regression was used to calculate IRs and incidence rate ratios (IRRs), overall and stratified by sex. Kaplan-Meier curves were plotted.

    Results: In total 807 (7.0%) of patients with AS and 3201 (5.5%) of matched controls had a history of prior fracture within a 6-year period, and were excluded from further analyses. We noted higher IRs for any fracture, VF and other MOF in AS vs controls, see Figure for Kaplan-Meier curves and Table for IRs and IRRs. In sex-stratified analyses, men with AS (vs. male controls) had a higher relative risk for all fracture outcomes, whereas among women with AS (vs. female controls), a higher relative risk was demonstrated for any fracture and VF. 5-year cumulative incidence for any fracture, VF and other MOF was 6.2%, 1.6% and 1.7%, respectively in AS and 4.3%, 0.3% and 1.2%, respectively in controls.

  • 30. Bengtsson, K.
    et al.
    Klingberg, E.
    Deminger, A.
    Jacobsson, L. T.
    Bergfeldt, L.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Göteborg.
    Ankylosing spondylitis related factors predict the presence of cardiac conduction disturbances: a swedish longitudinal cohort study2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, p. 337-338Article in journal (Other academic)
  • 31. Bengtsson, K.
    et al.
    Klingberg, E.
    Deminger, A.
    Jacobsson, L. T. H.
    Bergfeldt, L.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    CARDIAC CONDUCTION DISTURBANCES IN PATIENTS WITH ANKYLOSING SPONDYLITIS - A SWEDISH LONGITUDINAL COHORT STUDY2018In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, no 4, p. 714-714Article in journal (Other academic)
  • 32.
    Bengtsson, Karin
    et al.
    Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Rheumatology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Deminger, Anna
    Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Rheumatology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
    Klingberg, Eva
    Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Rheumatology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
    Dehlin, Mats
    Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Rheumatology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
    Exarchou, Sofia
    Department of Clinical Sciences, Lund University, Rheumatology, Malmö, Sweden.
    Lindström, Ulf
    Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Rheumatology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
    Askling, Johan
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Jacobsson, Lennart T H
    Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Comment on: Incidence of extra-articular manifestations in AS, PsA and undifferentiated SpA:: results from a national register-based cohort study. Reply2021In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 61, no 1, p. e31-Article in journal (Refereed)
  • 33. Bengtsson, Karin
    et al.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Lie, Elisabeth
    Klingberg, Eva
    Dehlin, Mats
    Exarchou, Sofia
    Lindstrom, Ulf
    Askling, Johan
    Jacobsson, Lennart T. H.
    Are Ankylosing Spondylitis, Psoriatic Arthritis and Undifferentiated Spondylarthritis Associated with an Increased Risk of Cardiovascular Disease?2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, article id 1057Article in journal (Other academic)
  • 34. Bengtsson, Karin
    et al.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Lie, Elisabeth
    Klingberg, Eva
    Dehlin, Mats
    Exarchou, Sofia
    Lindstrom, Ulf
    Askling, Johan
    Jacobsson, Lennart T. H.
    Increased Risk of Atrioventricular Block, Atrial Fibrillation and Pacemaker Implantation in Ankylosing Spondylitis, Undifferentiated Spondylarthritis and Psoriatic Arthritis Compared to the General Population2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no 10, article id 1059Article in journal (Other academic)
  • 35. Bengtsson, Karin
    et al.
    Jacobsson, Lennart T H
    Rydberg, Barbro
    Kvist, Göran
    Torstenson, Tomas
    Dehlin, Mats
    Hilme, Elisabet
    Lindhé, Anna
    Wallerstedt, Susanna Maria
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Box 480, S-405 30, Gothenburg, Sweden..
    Comparisons between comorbid conditions and health care consumption in rheumatoid arthritis patients with or without biological disease-modifying antirheumatic drugs: a register-based study2016In: BMC Musculoskeletal Disorders, E-ISSN 1471-2474, Vol. 17, no 1, article id 499Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Symptoms and prognosis of patients with rheumatoid arthritis (RA) have improved with more intensive therapy, including the biological disease-modifying anti-rheumatic drugs (bDMARDs). Real life data concerning how comorbidities are distributed among patients treated or not treated with bDMARDs are scarce. Our objective was to investigate differences in comorbidity and health care consumption in RA patients, with and without bDMARDs.

    METHODS: This cross-sectional study was performed in the Southwestern part of Sweden. Patients, aged ≥ 18 years and diagnosed with RA in secondary health care during 2009-2010, were identified in the regional health care database. Aggregated data of comorbidity and health care consumption were retrieved between 2006 and 2010. RA patients treated with bDMARDs on 31st December 2010 were identified in the Swedish Rheumatology Quality Register (SRQ), which includes the biologics register Anti-Rheumatic Therapy in Sweden (ARTIS). Descriptive, comparative, univariate and multiple logistic regression analyses were used to identify factors associated with bDMARDs.

    RESULTS: Seven thousand seven hundred and twelve (7712) RA patients were identified (age 64.8 ± 14.9 years, women 74.3%), of whom 1137 (14.7%) were treated with bDMARDs. Overall, the most common comorbidities were infections (69.2%), hypertension (41.1%), chronic respiratory disease (15.3%), ischemic heart disease (14.0%) and malignancy (13.7%). Patients without bDMARDs were older and had more comorbidity. In the multiple logistic regression analysis, older age, cerebrovascular and chronic respiratory disease, heart failure, depression and malignancy were all associated with no present bDMARDs. Infections were associated with bDMARDs. Patients treated with bDMARDs consumed more secondary outpatient care but less visits in primary health care compared to patients without bDMARDs.

    CONCLUSIONS: Patients treated with bDMARDs versus no bDMARDs were younger and had significantly lower period prevalence for most common comorbidities, with the exception of infections. Differences in comorbidities between RA patients with or without bDMARDs should be taken into consideration when evaluating effectiveness and safety of bDMARDs in ordinary care.

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  • 36. Bengtsson, Karin
    et al.
    Klingberg, Eva
    Deminger, Anna
    Wallberg, Hanna
    Jacobsson, Lennart T. H.
    Bergfeldt, Lennart
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Cardiac conduction disturbances in patients with ankylosing spondylitis: results from a 5-year follow-up cohort study2019In: RMD Open, E-ISSN 2056-5933, Vol. 5, no 2, article id e001053Article in journal (Refereed)
    Abstract [en]

    Objectives: To describe electrocardiographic (ECG) development in patients with ankylosing spondylitis (AS) and identify associations between baseline characteristics and cardiac conduction disturbances (CCD) at 5-year follow-up.

    Methods: In a longitudinal cohort study, 172 patients (54% men, mean age (SD) of 50 (13) years at baseline) with AS underwent ECG, physical examination, questionnaires and laboratory testing at baseline and at 5-year follow-up. Descriptive statistics and univariate and age- and sex-adjusted logistic regression analyses were used. CCD included both atrioventricular and intraventricular blocks.

    Results: Twenty-three of the 172 patients (13.4%) had a CCD at follow-up. Eight patients had developed a new CCD and eight had normalised their ECG. In the age- and sex-adjusted analyses, CCD at baseline (OR 24.8, 95% CI 7.3 to 84.5), male sex (OR 6.4, 95% CI 2.0 to 20.8), history of anterior uveitis (OR 4.4, 95% CI 1.3 to 14.5), higher ASDAS-CRP (OR 2.3, 95% CI 1.3 to 4.0), greater waist circumference (OR 1.3, 95% CI 1.1 to 1.6, per 5 cm), and medication with antiplatelets (OR 7.0, 95% CI 1.5 to 31.8) and beta-blockers (OR 3.4, 95% CI 1.0 to 11.5) were associated with a CCD at follow-up. Higher age and longer symptom duration were highly correlated and were both associated with a CCD at follow-up.

    Conclusions: The presence of CCD in AS is in part dynamic and associated with both AS and non-AS characteristics. Our results suggest that patients especially prone to present with CCDs are older men with a previous CCD, longer symptom duration, higher AS disease activity, a history of anterior uveitis and medication reflecting cardiovascular disease.

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  • 37.
    Berglin, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Lorentzon, Ronnie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Nordmark, L
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nilsson-Sojka, Birgitta
    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.
    Predictors of radiological progression and changes in hand bone density in early rheumatoid arthritis2003In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 42, no 2, p. 268-275Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To identify predictors for radiological and functional outcome and bone loss in the hands in early rheumatoid arthritis (RA) during the first 2 yr of disease and to study the relationship between these variables.

    METHODS: An inception cohort of consecutively recruited patients was examined at baseline and after 12 and 24 months using X-rays of hands and feet, clinical [28-joint count, Health Assessment Questionnaire (HAQ), global visual analogue scale (VAS), grip strength] and laboratory (erythrocyte sedimentation rate, C-reactive protein, markers of bone formation and resorption) measurements and dual-energy X-ray absorptiometry measurements of the hands.

    RESULTS: Joint destruction increased significantly during the study, with the Larsen score at baseline as the strongest predictor. Radiological progression and bone loss over 24 months were significantly retarded in patients responding to therapy. The effects of the shared epitope and initial high inflammatory activity on radiological progression were overridden by the therapeutic response. Radiological progression correlated significantly with bone loss. Global VAS, Larsen score and HAQ at inclusion significantly predicted change in HAQ over time.

    CONCLUSIONS: Radiological progression and bone loss were retarded by early therapeutic response. Bone loss was related to radiological progression.

  • 38.
    Berglin, Ewa
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Carlsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Effect of hydrogen sulfide on the mutagenicity of hydrogen peroxide in Salmonella typhimurium strain TA1021986In: Mutation research, ISSN 0027-5107, E-ISSN 1873-135X, Vol. 175, no 1, p. 5-9Article in journal (Refereed)
  • 39.
    Berglin, Ewa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Dahlqvist, J.
    Sjowall, J.
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lejon, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Mohammad, A. J.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Protein profiling in individuals before onset of anca-associated vasculitis2020In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 79, p. 372-372Article in journal (Other academic)
  • 40.
    Berglin, Ewa H.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Rantapää-Dahlqvist, Solbritt M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Does Evaluation Of Hand Bone Loss By Digital x-Ray Radiogrammetry Within The First 3 Months After Diagnosis Of Rheumatoid Arthrits Identify Patients At Risk For Radiological Progression?2013In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, no Special issue, Supplement 10, p. S834-S834, Meeting Abstract: 1958Article in journal (Other academic)
  • 41.
    Berglin, Ewa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Johansson, T.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sundin, U.
    Jidell, Erik
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Hallmans, Göran
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset2006In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 65, no 4, p. 453-458Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression. METHODS: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients) and were identified from among blood donors within the Medical Biobank of northern Sweden. Disease activity (erythrocyte sedimentation rate (ESR), C reactive protein, joint score, global visual analogue scale) and radiological destruction in hands and feet (Larsen score) were assessed at baseline and after two years. Anti-CCP antibodies and RFs were analysed using enzyme immunoassays. HLA shared epitope (SE) alleles (DRB1*0401/0404) were identified. RESULTS: Patients with anti-CCP antibodies before disease onset had significantly higher Larsen score at baseline and after two years. In multiple regression analyses baseline values of anti-CCP/IgA-RF/IgG-RF/IgM-RF, swollen joint count, and Larsen score significantly predicted radiological outcome at two years. In logistic regression analyses, baseline values of anti-CCP antibodies/IgA-RF, therapeutic response at six months, and swollen joint count/ESR significantly predicted radiological progression after two years. The baseline titre of anti-CCP antibodies was higher in patients with radiological progression and decreased significantly in those with response to therapy. SE allele carriage was associated with a positive test for anti-CCP antibodies in pre-patients and in early rheumatoid arthritis. CONCLUSIONS: Presence of anti-CCP antibodies before disease onset is associated with more severe radiological damage. The titre of anti-CCP antibodies is related to disease severity.

  • 42.
    Berglin, Ewa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Mohammad, A. J.
    Dahlqvist, J.
    Eriksson, C.
    Umeå University.
    Sjöwall, J.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Anti-neutrophil cytoplasmatic antibodies predate symptom onset of anca-associated vasculitis: a case-control study2020In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 79, p. 1065-1066Article in journal (Other academic)
  • 43.
    Berglin, Ewa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Mohammad, Aladdin J.
    Department of Clinical Sciences/Rheumatology, Lund University, Lund, Sweden; Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
    Dahlqvist, Johanna
    Department of Medical Biochemistry and Microbiology, and Medical Sciences, Uppsala University, Uppsala, Sweden.
    Johansson, Linda
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Eriksson, Catharina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Sjöwall, Johanna
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Clinic of Infectious Diseases Linköping University Hospital, Linköping, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis: a case-control study2021In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 117, article id 102579Article in journal (Refereed)
    Abstract [en]

    Objectives: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed.

    Methods: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples >1 month < 10 years from AAV symptom onset and two controls matched for sex, age, and sampling time for each case were included. Samples were screened using ELISAs for ANCA and further analysed for PR3-or MPO- specificities.

    Results: In ANCA-screen 35.7% of the pre-symptomatic cases and 3.5% of controls tested positive (p < 0.01). 26.2% of the cases were PR3-ANCA+ and 10.7% MPO-ANCA+. Median (Q1-Q3) predating time for PR3-ANCA+ was 2.7 (0.3–7.7) years and MPO-ANCA+ 2.0 (0.9–3.5) years. PR3-ANCA was demonstrated in samples up to nine years before symptom onset. At symptom onset predating PR3-ANCA+ cases were younger than PR3-ANCA- (P < 0.01), and MPO-ANCA+ were older than MPO-ANCA- (p < 0.05). Predating MPO-ANCA+ cases vs. MPO-ANCA- and vs. PR3-ANCA+ cases had more often at symptoms onset manifestations from lungs, kidneys or peripheral nervous system (p < 0.01 and p < 0.05, respectively).

    Conclusion: The PR3-and MPO-ANCAs are present years before AAV symptom onset and represent distinct diseases.

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  • 44.
    Berglin, Ewa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Padyukov, Leonid
    Sundin, Ulf
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Van Venrooij, Walther J
    Klareskog, Lars
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis2004In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 6, no 4, p. R303-R308Article in journal (Refereed)
    Abstract [en]

    Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis (RA) by years. A nested case–control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of shared epitope (SE) genes, defined as HLA-DRB1*0404 or DRB1*0401, and of anti-CCP antibodies and RFs in individuals who subsequently developed RA. Patients with RA were identified from among blood donors whose samples had been collected years before the onset of symptoms. Controls matched for age, sex, and date of sampling were selected randomly from the same cohort. The SE genes were identified by polymerase chain reaction sequence-specific primers. Anti-CCP2 antibodies and RFs were determined using enzyme immunoassays. Fifty-nine individuals with RA were identified as blood donors, with a median antedating time of 2.0 years (interquartile range 0.9–3.9 years) before presenting with symptoms of RA. The sensitivity for SE as a diagnostic indicator for RA was 60% and the specificity was 64%. The corresponding figures for anti-CCP antibodies were 37% and 98%, and for RFs, 17–42% and 94%, respectively. In a logistic regression analysis, SE (odds ratio [OR] = 2.35), anti-CCP antibodies (OR = 15.9), and IgA-RF (OR = 6.8) significantly predicted RA. In a combination model analysis, anti-CCP antibodies combined with SE had the highest OR (66.8, 95% confidence interval 8.3–539.4) in predicting RA, compared with anti-CCP antibodies without SE (OR = 25.01, 95% confidence interval 2.8–222.2) or SE without anti-CCP antibodies (OR = 1.9, 95% confidence interval 0.9–4.2). This study showed that the presence of anti-CCP antibodies together with SE gene carriage is associated with a very high relative risk for future development of RA.

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  • 45.
    Berglin, Ewa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Comparison of the 1987 ACR and 2010 ACR/EULAR classification criteria for rheumatoid arthritis in clinical practice: a prospective cohort study2013In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 42, no 5, p. 362-368Article in journal (Refereed)
    Abstract [en]

    Objective: To compare application of the 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for diagnosing rheumatoid arthritis (RA) in clinical practice. Method: The medical records of patients with early arthritis attending the Rheumatology Department, Umea University Hospital (n = 1026) were analysed. Patients with synovitis in at least one joint, no diagnosis other than RA being better for explaining the synovitis, and duration of symptoms less than 1 year at first visit, and at least 1 year of follow-up were included consecutively. Fulfilment of the 1987 and 2010 criteria at baseline was evaluated. Sensitivity and specificity for each criterion set, where estimated by using the outcome measures: initiation of methotrexate (MTX) therapy during the first year, and a clinical diagnosis of RA at the 1-year follow-up. Radiographs of hands and feet were evaluated using the Larsen score. Results: The study included 313 patients, of whom 56% fulfilled the 1987 ACR criteria, 74% the 2010 ACR/EULAR criteria, and 53% both sets of criteria at baseline. The sensitivity/specificity for the 1987 and 2010 criteria with MTX within the first year as the outcome measure was 0.68/0.79 and 0.84/0.54, respectively, and with a diagnosis of RA at follow-up 0.72/0.83 and 0.91/0.65, respectively. Older patients (i.e. >= 60 years) more often fulfilled the 2010 criteria. Patients who fulfilled the 2010 ACR/EULAR but not the 1987 ACR criteria had a lower Larsen score at inclusion and after 2 years. Conclusions: Compared with the 1987 ACR criteria, the 2010 ACR/EULAR criteria have higher sensitivity but lower specificity, especially in patients aged >= 60 years. The 1987 ACR criteria are suggested to predict a more erosive disease.

  • 46.
    Berglin, Ewa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Rantapää-Dahlqvist, Solbritt M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Comparison of the 1987 ACR and 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis in Clinical Practice2011In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 63, no 10, p. S117-S117Article in journal (Refereed)
  • 47. Berglund, S
    et al.
    Södergren, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Wållberg Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine: a six-year follow-up study2009In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 27, no 5, p. 822-825Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate whether homocysteine is linked to atherothrombotic (AT) events in patients with rheumatoid arthritis (RA). METHODS: Analysis of homocysteine (Hcy) levels was carried out in 235 consecutive RA patients. They were followed-up for 6.5 years or until death, with analysis of AT risk factors and the type and length of DMARD and corticosteroid treatment. The disease history before inclusion was collected. Six categories of AT events were defined. In addition, the diagnosis of the patients at follow-up was co-analyzed with the nationwide population-based Swedish Inpatient Register and Death Register to certify all events. RESULTS: The Hcy level was found to be higher in males (p<0.05) and increased with age (p<0.001). Patients with folic acid supplementation had significantly lower levels, while those on corticosteroids had higher levels. High Hcy levels predicted AT events (n=48) during a 6.5-year follow-up adjusted for age and male sex in a logistic regression analysis. CONCLUSION: In this study, RA patients on folic acid had lower Hcy levels. High Hcy levels (in addition to age, sex and diabetes) predicted AT event prospectively.

  • 48.
    Bjorsenius, I.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Rantapää-Dahlqvist, Solbritt
    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.
    Södergren, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Increased progression of atherosclerosis in patients with rheumatoid arthritis is partially reflected by disease severity at the time of diagnosis: 11-year prospective follow-up2018In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, p. 20-21Article in journal (Other academic)
  • 49. Björk, Albin
    et al.
    Mofors, Johannes
    Kvarnström, Marika
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Bucher, Sara Magnusson
    Hillert, Jan
    Eriksson, Per
    Mandl, Thomas
    Nordmark, Gunnel
    Alfredsson, Lars
    Wahren-Herlenius, Marie
    Cigarette smoking is a risk factor for developing primary Sjögren's syndrome with Ro/SSA and La/SSB autoantibodies2018In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, no 3, p. S330-S330Article in journal (Other academic)
  • 50.
    Björk, Mathilda
    et al.
    Linköping University, Norrköping, Sweden.
    Dragioti, Elena
    Linköping University, Linköping, Sweden.
    Alexandersson, Helene
    Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Esbensen, Bente Appel
    Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
    Boström, Carina
    Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Friden, Cecilia
    Karolinska Institutet, Huddinge, Sweden.
    Hjalmarsson, Sara
    Swedish Rheumatism Association, Stockholm, Sweden.
    Hörnberg, Kristina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Kjeken, Ingvild
    Diakonhjemmet Hospital, Vinderen, Oslo, Norway.
    Regardt, Malin
    Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Sundelin, Gunnevi
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Sverker, Annette
    Linköping University, Linköping, Sweden.
    Welin, Elisabet
    Örebro University, Örebro, Sweden.
    Brodin, Nina
    Karolinska Institutet, Huddinge, Sweden, and Danderyd Hospital Corporation, Stockholm, Sweden.
    Inflammatory Arthritis and the Effect of Physical Activity on Quality of Life and Self-Reported Function: A Systematic Review and Meta-Analysis2022In: Arthritis care & research, ISSN 2151-464X, E-ISSN 2151-4658, Vol. 74, no 1, p. 31-43Article, review/survey (Refereed)
    Abstract [en]

    Objective: Although physical activity is an evidence-based intervention that reduces disease-related symptoms and comorbidity in rheumatoid arthritis (RA), the effect of physical activity on self-reported function and quality of life (QoL) has not yet been analyzed. The present study synthesizes the evidence for the effectiveness of physical activity on QoL and self-reported function in adults with RA, spondyloarthritis (SpA), and psoriatic arthritis (PsA).

    Methods: The databases PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify relevant randomized controlled trials (RCTs). Screening, risk of bias assessment (using the RoB 2.0 tool), and data extraction were independently performed by 2 or more of the authors. Meta-analyses were conducted with a random-effects model.

    Results: Systematic review included 55 RCTs, and meta-analysis included 37 RCTs. Of the 55 studies included, 76%, 20%, and 4% were designed to investigate RA, SpA, and PsA, respectively. In the RA studies, effects of physical activity on QoL and function were found compared to the group of inactive controls; no effects were found compared to the group of active controls. In the SpA studies, the effects of physical activity on QoL were in favor of the control group. Effects of physical activity on function were found compared to the group of inactive controls and sustained in fatigue and pain when compared to the group of active controls. In the PsA studies, no effects on QoL were found, but effects on function were noted when compared to the group of inactive controls. The effect size was below 0.30 in the majority of the comparisons.

    Conclusion: Physical activity may improve QoL and self-reported function in individuals with RA, SpA, and PsA. However, larger trials are needed, especially in SpA and PsA.

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