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  • 1. Bertilsson, Lennart
    et al.
    Andersson-Gäre, Boel
    Fasth, Anders
    Petersson, Ingemar F
    Forsblad-D'elia, Helena
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Disease course, outcome, and predictors of outcome in a population-based juvenile chronic arthritis cohort followed for 17 years.2013In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 40, no 5, p. 715-24Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate disease course, outcome, and predictors of outcome in an unselected population-based cohort of individuals diagnosed with juvenile chronic arthritis (JCA) followed for 17 years.

    METHODS: The cohort consisted of 132 incidence JCA cases identified 1984-1986 according to EULAR criteria. At 5-year followup, 129 individuals underwent joint assessment, laboratory measurements, radiographic examination, and medication and functional assessment. At 17-year followup, 86 were examined with joint assessment, laboratory measurements, medication assessment, Health Assessment Questionnaire (HAQ), Keitel functional test (KFT), and Medical Outcomes Study Short Form-36 (SF-36).

    RESULTS: At 17-year followup, 40% were in remission, 44% changed subgroups, median HAQ score was 0.0 (range 0.0-1.5), and median KFT was 100 (range 54-100). SF-36 scores were significantly lower compared to a reference group. Thirty-nine percent of those in remission at 5-year followup were not in remission at 17-year followup. In multivariate analyses of variables from the 17-year followup: remission was predicted by remission at 5-year followup (OR 4.8); HAQ > 0 by rheumatoid factor (RF)-positivity at 5-year followup (OR 3.6); KFT < 100 by nonremission (OR 11.3); and RF-positivity (OR 5.6) at 5-year followup; and the SF-36 physical component summary score above average of the reference group by remission at 5-year followup (OR 5.8).

    CONCLUSION: This longterm study of 86 individuals with JCA showed large variability of disease courses and of impaired health-related quality of life. Sixty percent were not in remission at 17-year followup. Longterm outcome was best predicted by and associated with characteristics at 5-year followup rather than those at onset.

  • 2. Boström, Elisabeth Almer
    et al.
    d'Elia, Helena Forsblad
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Dahlgren, Ulf
    Simark-Mattsson, Charlotte
    Hasséus, Bengt
    Carlsten, Hans
    Tarkowski, Andrej
    Bokarewa, Maria
    Salivary resistin reflects local inflammation in Sjögren's syndrome.2008In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 35, no 10, p. 2005-11Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the role of resistin in primary Sjögren's syndrome (pSS) and its relation to local inflammation.

    METHODS: Blood and saliva were collected from 37 patients with pSS (duration of symptoms 12.6+/-1 yrs) and 32 healthy controls. Expression of resistin in salivary glands was visualized immunohistologically, and levels of resistin were detected by ELISA. Levels of resistin were evaluated at baseline and following oral dehydroepiandrosterone (DHEA) treatment (50 mg/day). The effect of DHEA treatment on the secretion of resistin was assessed in vitro in human leukocytes after challenge with insulin and lipopolysaccharide.

    RESULTS: Levels of resistin in saliva were significantly higher in patients with pSS than in controls, while circulating levels of resistin were similar in both groups. Resistin was expressed in the epithelial cells of striated ducts and in the lymphocytic foci. Resistin levels in saliva were related to the intensity of inflammation in the minor salivary glands of pSS patients. No changes of the levels of resistin in blood or saliva were observed during DHEA treatment. Exposure of naive leukocytes to DHEA in vitro induced significant expression of resistin compared to nonstimulated peripheral blood mononuclear cells (p=0.031).

    CONCLUSION: We showed that levels of resistin are upregulated locally in the salivary glands of patients with pSS; and that the levels of resistin correspond to the intensity of lymphocytic inflammation in patients with pSS. We suggest that resistin is expressed in the salivary glands of patients with pSS and may be a driving factor of local inflammation.

  • 3. Cvetkovic, Jasmina Trifunovic
    et al.
    Wållberg-Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Lefvert, Ann Kari
    Susceptibility for and clinical manifestations of rheumatoid arthritis are associated with polymorphisms of the TNF-alpha, IL-1 beta, and IL-lRa genes2002In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 29, no 2, p. 212-219Article in journal (Refereed)
    Abstract [en]

    Objective. To analyze the association of genetic polymorphisms of pro-inflammatory cytokines with rheumatoid arthritis (RA) in comparison with healthy controls from Northern Sweden and the potential contribution of these genetic variants for disease severity and development of cardiovascular complications.

    Methods. Polymerase chain reaction amplification was used for analysis of TaqI restriction fragment length polymorphism (RFLP) of interleukin-1 beta (IL-1beta), variable tandem repeat polymorphism of IL-1 receptor antagonist (IL-1Ra) gene and NcoI RFLP at position -308 of tumor necrosis factor-alpha (TNF-alpha) gene, One hundred and fifty-four patients with RA, 42 men and 112 women, were consecutively recruited into the study through the Department of Rheumatology.

    Results. The allele A1 of TNF-alpha was more common in the patient group (p < 0.01 OR = 1.62). Patients having the genotype A1A2 seemed to develop more severe disease compared with patients with A1A1 genotype: they were younger at disease onset (p < 0.05), had a higher accumulated disease activity (p < 0.05) and worse functional class (p < 0.05), Patients with genotype A2A2 of IL-1beta had higher accumulated disease activity score than patients with A1A1 and A1A2 (p < 0.05). The allelic combination A1 IL-1beta/A2 IL-1Ra was less prevalent in RA patients who developed cardiovascular complications (p < 0.005 OR = 0.20).

    Conclusions. The A1 allele of TNF-alpha associates with RA. Genotypes A1A2 of TNF-alpha and A2A2 of IL-1beta are associated with more severe disease. The allelic combination A1 IL-1beta/A2 IL-1Ra is less often present in RA patients who developed cardiovascular complications.

  • 4.
    Dahlqvist, Solbritt Rantapää
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Nordmark, LG
    Bjelle, Anders
    HLA-B27 and involvement of sacroiliac joints in rheumatoid-arthritis1984In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 11, no 1, p. 27-32Article in journal (Refereed)
    Abstract [en]

    The frequency of radiographic signs of sacroiliac joint involvement (greater than or equal to 2 and greater than or equal to 3 according to the New York criteria) was significantly higher in 28 HLA-B27 positive patients with classical seropositive rheumatoid arthritis (RA), than in 28 B27 negative RA controls. The B27 positive RA patients had more subcutaneous nodules (p less than 0.01), worse functional class (p less than 0.05), and higher levels of erythrocyte sedimentation rate (ESR) (p less than 0.05) and haptoglobin (p less than 0.05). Sacroiliitis, independent of HLA-B27, was associated with higher levels of ESR (p less than 0.05), and with a higher frequency of positive ANA test (p less than 0.05). It is neither related to the functional class nor to the duration of the disease

  • 5.
    Dahlqvist, Solbritt Rantapää
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Ström, Håkan
    Bjelle, Anders
    Möller, Erna
    HLA haplotypes in a family with ankylosing-spondylitis and rheumatoid-arthritis1985In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 12, no 3, p. 518-522Article in journal (Refereed)
    Abstract [en]

    HLA haplotypes (including A, B, C and DR loci) were studied in a family with members who had both rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Sacroiliitis was found in 7 family members, one of whom had AS and 2 others erosive, seropositive RA. They carried the B27-DR4 haplotype, suggesting a possible dual genetic association of the same haplotype in both RA and AS. Three other different HLA-B27 containing haplotype were found, 2 of which could be associated with sacroiliitis/AS. Within this family sacroiliitis and/or AS rather seemed associated with the B27 antigen itself than with the same haplotype.

  • 6.
    D'Elia, Helena Forsblad
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Larsen, Arvi
    Mattsson, Lars-Ake
    Waltbrand, Eva
    Kvist, Göran
    Mellström, Dan
    Saxne, Tore
    Ohlsson, Claes
    Nordborg, Elisabeth
    Carlsten, Hans
    Influence of hormone replacement therapy on disease progression and bone mineral density in rheumatoid arthritis.2003In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 30, no 7, p. 1456-63Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Hormone replacement therapy (HRT) is known to exert a positive effect in preventing bone loss and a beneficial effect on the disease activity in rheumatoid arthritis (RA). We evaluated the effects of HRT on bone mineral density (BMD) and on the course of established RA.

    METHODS: Eighty-eight postmenopausal women with RA were randomly allocated to receive HRT, vitamin D3, and calcium supplementation or vitamin D3 and calcium supplementation alone for 2 years. The effects of additional HRT on laboratory and clinical measures of disease activity, quality of life, and BMD and on radiographic joint damage were investigated.

    RESULTS: Treatment with HRT suppressed signs of inflammation as shown by reduction in erythrocyte sedimentation rate (ESR) (p = 0.025) and an elevation in hemoglobin concentration (p = 0.007), a better clinical outcome assessed by response on the Disease Activity Score 28 (DAS28) (p = 0.036), increased BMD in the forearm, proximal femur and spine (p < 0.01), and retarded (p = 0.026) progression of joint destruction among patients with radiological progressive disease. No significant effect on quality of life was seen.

    CONCLUSION: Two years of HRT in women with active RA had significant ameliorating effects on inflammation, DAS28 response, and BMD and was associated with slower progression of radiological joint destruction. The mechanisms by which HRT exerts its effects remain to be elucidated. We suggest HRT can be used in addition to conventional therapy in the management of postmenopausal patients with RA.

  • 7. Elert, J
    et al.
    Dahlqvist, Solbritt Rantapää
    Almay, B
    Eisemann, M
    Muscle endurance, muscle tension and personality-traits in patients with muscle or joint pain - a pilot-study1993In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 20, p. 1550-1556Article in journal (Refereed)
    Abstract [en]

    Objective. To investigate the relationships between personality traits, depressive symptomatology and continuous muscle tension. Methods. These were investigated by means of a visual analog scale and the presence of continuous muscle tension during repeated isokinetic shoulder flexions in patients with muscle or joint pain and controls. Results. A significantly higher level of muscle tension between contractions was found in the patient groups in painful muscles. The patients with primary fibromyalgia and trapezius myalgia differed in degree of depressive symptomatology compared to controls. Conclusion. Inhibition of aggression correlated significantly with the tension level between contractions during the isokinetic test indicating interaction between psychological and somatic factors.

  • 8.
    Eurenius, Eva
    et al.
    Verksamhetsutvecklingsstaben - Vård och hälsa, Västerbottens läns landsting.
    Brodin, Nina
    Lindblad, Staffan
    Opava, Christina H
    Predicting physical activity and general health perception among patients with rheumatoid arthritis2007In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 34, no 1, p. 10-15Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe changes over one year in physical activity, body functions, and disease activity in patients with rheumatoid arthritis (RA) and to identify predictors for physical activity and general health perception.

    METHODS: One hundred two patients with RA were recruited for the study (median age 57 yrs, range 19-84; median disease duration 15 mo, range 4-78; 76% women). Self-reported data on physical activity and health locus of control, tests of lower extremity function, grip force, joint range of motion, balance, and measures of disease activity, including pain, general health perception, Health Assessment Questionnaire (HAQ), and Disease Activity Score (DAS28), were collected on 2 occasions, one year apart. Each variable was dichotomized to fit logistic regression models, performed to identify which variables predicted physical activity and general health perception over one year.

    RESULTS: Physical activity was stable, while lower extremity function, grip force, and range of motion improved and DAS28 decreased significantly over one year. A high physical activity level at baseline was the only predictor of high physical activity (odds ratio 3.85, 95% confidence interval 1.67-9.09) one year later. Low pain (OR 8.47, 95% CI 2.97-24.39), high physical activity (OR 3.72, 95% CI 1.39-10.10), and good lower extremity function (OR 2.94, 95% CI 1.04-8.33) were identified as predictors of good general health perception.

    CONCLUSION: While pain is a well known predictor of general health perception, to our knowledge, this is the first study to identify predictive factors related to physical activity and lower extremity function as important for perceived health among patients with RA.

  • 9. Geijer, Mats
    et al.
    Lindqvist, Ulla
    Husmark, Tomas
    Alenius, Gerd-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Larsson, Per T.
    Teleman, Annika
    Theander, Elke
    The Swedish Early Psoriatic Arthritis Registry 5-year Followup: Substantial Radiographic Progression Mainly in Men with High Disease Activity and Development of Dactylitis2015In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 11, p. 2110-2117Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 10.
    Haapala, Jussi
    et al.
    Department of Surgery, Kuopio University Hospital, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Inkinen, Ritva
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Parkkinen, Jyrki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Ågren, Ulla
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Arokoski, Jari
    Department of Physical and Rehabilitation Medicine, Kuopio University Hospital, Kuopio, Finland.
    Kiviranta, Ilkka
    Department of Surgery, Kuopio University Hospital, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Markku
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Coordinated regulation of hyaluronan and aggrecan content in the articular cartilage of immobilized and exercised dogs.1996In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 23, no 9, p. 1586-1593, article id 8877929Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the influence of joint loading and immobilization on articular cartilage hyaluronan concentration and histological distribution in the knee joints of young dogs subjected to 11 weeks' immobilization by splinting, and 15 weeks' running exercise at a rate of 40 km/day.

    METHODS: The amount of hyaluronan in articular cartilage was determined by a competitive binding assay using a biotinylated hyaluronan binding complex (HABC) of aggrecan and link protein. Histologic sections were stained for the localization of hyaluronan with the HABC probe. Extracted proteoglycans were characterized by sodium dodecyl sulfate agarose gel electrophoresis.

    RESULTS: Immobilization significantly reduced the concentration of hyaluronan in all sites studied (tibial and femoral condyles, patellar surface of femur). The proportion of hyaluronan to total uronic acid (mainly from aggrecan) remained unchanged because of a concurrent decrease in aggrecan. The ratio of hyaluronan and aggrecan remained constant also in runners. The staining pattern of free hyaluronan in the tissue sections and the electrophoretic mobility of the extracted proteoglycans were not affected by the different loading regimes.

    CONCLUSION: Reduced joint loading due to splint immobilization significantly decreases both hyaluronan and aggrecan in the articular cartilage. The remarkably parallel changes in aggrecan and hyaluronan content suggest that joint loading exerts a coordinated influence on their metabolism.

  • 11. Helliwell, Philip S
    et al.
    Taylor, William J
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Alenius, Gerd-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Treatment of psoriatic arthritis and rheumatoid arthritis with disease modifying drugs: comparison of drugs and adverse reactions2008In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 35, no 3, p. 472-476Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory diseases of the musculoskeletal system. Although it seems likely that these conditions have a different pathogenesis, the drugs used to treat them are the same. Our study used a cross-sectional clinical database to compare drug use and side-effect profile in these 2 diseases. METHODS: The CASPAR study collected data on 588 patients with PsA and 536 controls, 70% of whom had RA. Data on disease modifying drug treatments used over the whole illness were recorded, together with their outcomes, including adverse events, for RA and PsA. RESULTS: For both diseases methotrexate (MTX) was the most frequently used disease modifying drug (39% of patients with PsA, 30% with RA), with over 70% of patients in both diseases still taking the drug. Other drugs were used with the following frequencies in PsA and RA, respectively: sulfasalazine 22%/13%, gold salts 7%/11%, antimalarial drugs 5%/14%, corticosteroids 10%/17%, and anti-tumor necrosis factor (TNF) drugs 6%/5%. Compared to RA, cyclosporine and anti-TNF agents were less likely to be ineffective in PsA. Compared to RA, subjects with PsA were less likely to be taking MTX and more likely to be taking anti-TNF agents. Hepatotoxicity with MTX was more common in PsA and pulmonary toxicity with MTX was found more often in RA. CONCLUSION: These data provide insight into prescribing patterns of disease modifying drugs in RA and PsA in a large international cohort, together with the differential adverse events of these drugs between these diseases.

  • 12.
    Inkinen, Ritva
    et al.
    Department of Anatomy, University of Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Finland.
    Lehmonen, Sirpa
    Department of Anatomy, University of Kuopio, Finland.
    Puustjärvi, Kaija
    Department of Anatomy, University of Kuopio, Finland.
    Kääpä, Eeva
    Department of Physical Medicine and Rehabilitation,Helsinki University Hospital, Helsinki, Finland.
    Tammi, Markku
    Department of Anatomy, University of Kuopio, Finland.
    Relative increase of biglycan and decorin and altered chondroitin sulfate epitopes in the degenerating human intervertebral disc.1998In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 25, no 3, p. 506-514, article id 9517772Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Proteoglycans are major components of the extracellular matrix of the intervertebral disc. They are vital for the biomechanical properties of the tissue, and are subject to changes in disc degeneration. We aimed to further define these changes and their relationship to normal aging.

    METHODS: Normal discs (age 13-53 years, n = 6) were analyzed from 5 different sites across the sagittal anterior-posterior direction. Degenerated anterior annulus fibrosus was collected from 7 patients aged 39-46 years. Extracted proteoglycans were separated using agarose and polyacrylamide gel electrophoresis and detected with toluidine blue staining and Western blotting.

    RESULTS: The center of the disc showed the highest level of total proteoglycans, but lowest levels of decorin and biglycan. Western blots displayed reduced signal for both glycanated and nonglycanated biglycan and decorin after adolescence, while an increased signal of biglycan was observed in degenerated annuli. The 7D4(-) and 3B3(-) epitopes on native chondroitin sulfate chains were present in the large proteoglycans of intervertebral discs, but their signal intensity had no correlation to degeneration. Chondroitinase ABC digestion of the blots brought up 7D4(+) signal in the small proteoglycans of degenerated, but not in healthy tissue. Decrease or total loss of 2B6(+) epitope (indicating 4-sulfated stubs of chondroitin sulfate chains) were found in the large proteoglycans of all degenerated annuli.

    CONCLUSION: Human intervertebral disc degeneration involves the accumulation of decorin and biglycan relative to other uronic acid containing proteoglycans, the disappearance of 4-sulfated core region in aggrecan-like large proteoglycans, and the emergence of a core structure in the chains of small proteoglycans reacting with the 7D4 antibody; these findings indicate a fundamental alteration in matrix properties that may contribute to the pathogenesis of the disease.

  • 13.
    Innala, Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Kokkonen, Heidi
    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.
    Jidell, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Berglin, Ewa
    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.
    Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides2008In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 35, no 6, p. 1002-1008Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the predictive values for disease progression of various antibodies against citrullinated peptide proteins (ACPA) and their relation to PTPN22 1858C/T polymorphism and HLA-DRB1 alleles in early rheumatoid arthritis (RA).

    METHODS: The ACPA, e.g., antibodies against mutated citrullinated vimentin (MCV), cyclic citrullinated peptides (CCP) type 2 and 3 (both of IgG isotype) and 3.1 (of both IgG and IgA isotypes), were analyzed at baseline in patients with early RA (n = 210) and in population controls (n = 102) using an enzyme immunoassay. A receiver-operating characteristic curve was constructed for each antibody. Disease activity [swollen and tender joints, visual analog scale for global health, and erythrocyte sedimentation rate (ESR)] was evaluated at baseline and regularly for 24 months. Radiographs of hands and feet were graded using the Larsen score.

    RESULTS: Patients with anti-MCV antibodies had significantly less reduction in Disease Activity Score (DAS28) over time (p < 0.01), and significantly increased area under the curve (AUC) for DAS28 (p < 0.05), ESR (p < 0.01), C-reactive protein (p < 0.01), and swollen joint count (p = 0.057) compared to those without. Corresponding differences were not found in patients with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression (p < 0.0001-0.01) and radiological outcome (p < 0.0001-0.01) at 24 months were significantly predicted by all ACPA after baseline adjustments. PTPN22 T variant and HLA-DRB1 alleles were not related to radiological progression or inflammatory activity over time.

    CONCLUSION: Anti-MCV antibodies are associated with a more severe RA disease, as measured by DAS28, ESR, and swollen joint count over time, compared with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression was predicted equally by all 4 autoantibodies.

  • 14. Jin, Tao
    et al.
    Almehed, Katarina
    Zhu, Yihong
    Carlsten, Hans
    Forsblad-d'Elia, Helena
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Soluble E-cadherin in systemic lupus erythematosus.2013In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 40, no 10, p. 1677-82Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: E-cadherin is a potent adherens junction molecule implicated in tissue morphogenesis, epithelial functioning, and immune regulation. Serum levels of soluble E-cadherin (sE-cadherin), an end product of proteolytic cleavage of E-cadherin, is increased in patients with cancer, infections, and inflammation-related diseases. The aim of our study was to measure serum levels of sE-cadherin in systemic lupus erythematosus (SLE) and to determine associations between serum levels of sE-cadherin and markers of inflammation and organ damage in female patients with SLE.

    METHODS: Serum levels of sE-cadherin were analyzed by ELISA in 150 female patients with SLE and 31 healthy women. Simple and multiple regression analyses between sE-cadherin levels and disease-related variables were performed in patients with SLE.

    RESULTS: Serum levels of sE-cadherin were elevated in patients with SLE compared with levels in healthy controls. sE-cadherin levels correlated positively with age, disease duration, SLE Collaborating Clinics Damage Index, erythrocyte sedimentation rate (ESR), s-creatinine, cholesterol, triglycerides, interleukin 6, and matrix metalloproteinase-3. In multiple regression analysis, s-creatinine, age, ESR, and triglycerides remained determinants of sE-cadherin. Within the patients with SLE, higher sE-cadherin levels were found only in patients with renal damage, i.e., s-creatinine > 90 μmol/l, glomerular filtration rate < 50 ml/min, or renal involvement ever by SLE.

    CONCLUSION: Our study demonstrates significantly elevated serum levels of sE-cadherin in women with SLE compared with healthy women. The levels of sE-cadherin were positively correlated to s-creatinine, age, ESR, and triglycerides. Significantly elevated sE-cadherin levels were observed only in patients with renal damage.

  • 15. Jonsson, S W
    et al.
    Backman, C
    Johnson, O
    Karp, K
    Lundstrom, E
    Sundqvist, K G
    Dahlqvist, Solbritt Rantapää
    Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis2001In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 28, p. 2597-2602Article in journal (Refereed)
    Abstract [en]

    Objective. To measure the extent of atherosclerosis in patients with rheumatoid arthritis (RA) with a disease duration of considerable length, and in age and sex matched individuals. Methods. Thirty-nine patients with RA (30 women, 9 men) with disease onset occurring between 1974 and 1978, and less than 65 years of age at the time of investigation, were enrolled together with 39 sex and age matched controls. Quantitative measurement of intima-media thickness (IMT) and semiquantitative assessment of the presence of plaque were undertaken by B-mode ultrasound of the common carotid artery (CCA-IMT) and the common femoral artery on the right-hand side. Echo Doppler cardiography was performed with an Accuson Aspen. The results were related to disease activity variables and accumulated disease activity, to lipid levels [i.e., cholesterol, high density lipoproteins, low density lipoproteins, triglycerides (TG)], to hemostatic factors [tissue plasminogen activator antigen (tPAag), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF)], and to soluble adhesion molecules (sICAM-1 and sE-selectin). Results. Patients with RA had higher maximal and mean IMT values compared with controls. The difference concerning mean CCA-IMT reached statistical significance in patients with RA and correlated significantly with lipids (cholesterol, LDL, LDL/HDL ratio, TG) and tPAag. The prevalence of plaques, as well as of aortic cusp sclerosis, was higher in RA but only the difference in aortic cusp sclerosis was statistically significant. Patients with plaques had significantly higher levels of lipids (cholesterol, LDL, LDL/HDL ratio) than patients without plaques, while patients with cusp sclerosis had significantly higher cholesterol and TG levels. sICAM-1 was significantly higher both in patients with plaques and in those with aortic cusp sclerosis compared to patients without. Conclusion. Our results suggest an accelerated atherosclerosis in patients with RA that is related mainly to lipid levels.

  • 16.
    Juneblad, Kristina
    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.
    Alenius, Gerd-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Disease activity and increased risk of cardiovascular death among patients with psoriatic arthritis2016In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 43, no 12, p. 2155-2161Article in journal (Refereed)
    Abstract [en]

    Objective: Recent studies indicate increased cardiovascular (CV) morbidity and mortality in patients with psoriatic arthritis (PsA), but results are inconsistent. This prompted our investigation of the mortality rate, cause of death, and incidence of acute CV events in patients from northern Sweden with PsA.

    Methods: Patients with established PsA (464) were included. To calculate standardized mortality ratio (SMR) and standardized incidence ratio (SIR) for CV events, data were extracted from the National Causes of Death Register and the National Inpatient Care Register in Sweden, and compared with the general population. The study period was 1995-2011. To study the effect of inflammatory activity, a composite disease activity index (DAI) was used.

    Results: The SMR (95% CI) for overall mortality and diseases of the circulatory system (International Classification of Diseases, 10th edition; I00-I99) was 1.22 (0.89-1.63) and 1.64 (1.02-2.52), respectively. In regression analysis, DAI was significantly associated with death (OR 1.99, 95% CI 1.41-2.80) when adjusted for age and sex (p < 0.001), and remained significant after stratifying patients into the 2 major causes of death: diseases of the circulatory system and malignant neoplasms. Peripheral and axial disease was associated with death (OR 4.02, 95% CI 1.84-8.84, p < 0.001) compared with peripheral disease only. The SIR (95% CI) for a CV event (myocardial infarction or stroke) was 0.597 (0.40-0.86); this association was only significant in men.

    Conclusion: Patients with PsA had a small but significant increase in SMR for death due to diseases of the circulatory system compared with the general population. Among patients, death was associated with DAI, as well as axial involvement in combination with peripheral disease, indicating more aggressive disease phenotypes.

  • 17. Kastbom, Alf
    et al.
    Ärlestig, Lisbeth
    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.
    Genetic Variants of the NLRP3 Inflammasome Are Associated with Stroke in Patients with Rheumatoid Arthritis2015In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 10, p. 1740-1745Article in journal (Refereed)
    Abstract [en]

    Objective. Inflammasomes are intracellular protein complexes important for the production of proinflammatory cytokines. Studies have suggested that the NLRP3 inflammasome influences both the severity of rheumatoid arthritis (RA) and development of atherosclerosis. Therefore, we investigated whether functional genetic variants related to the NLRP3 inflammasome influence the risk of cardiovascular (CV) disease (CVD) in patients with RA. Methods. The incidence of CVD was assessed in 522 patients with established RA by a retrospective survey of medical records in combination with a 6-year prospective followup. NLRP3-Q705K and CARD8-C10X genotypes were analyzed in relation to CVD by logistic regression, adjusting for traditional risk factors, antirheumatic treatment, and age at the onset of RA. Results. Carriage of the NLRP3-Q705K minor allele was associated with an increased risk of stroke/transient ischemic attack (TIA; OR 2.01, 95% CI 1.0-4.1, p = 0.05), while CARD8-C10X was not associated with any type of CV event. Patients with >= 1 variant allele in both polymorphisms had an increased risk of CVD when compared with patients without variant alleles present in both polymorphisms (adjusted OR 3.05, 95% CI 1.42-6.54, p = 0.004). Stratification showed that this risk was confined to stroke/TIA (adjusted OR 5.09, 95% CI 2.27-11.44, p < 0.0001) and not to myocardial infarction (MI)/angina pectoris (adjusted OR 1.58, 95% CI 0.67-3.73). Risk estimates were consistently higher among female patients. Conclusion. Genetic variants of the NLRP3 inflammasome influence the risk of stroke/TIA, but not of MI/angina pectoris in Swedish patients with established RA.

  • 18. Klingberg, Eva
    et al.
    Geijer, Mats
    Göthlin, Jan
    Mellström, Dan
    Lorentzon, Mattias
    Hilme, Elisabet
    Hedberg, Martin
    Carlsten, Hans
    Forsblad-D'Elia, Helena
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Vertebral fractures in ankylosing spondylitis are associated with lower bone mineral density in both central and peripheral skeleton.2012In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 39, no 10, p. 1987-95Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the prevalence and risk factors for vertebral fractures (VF) in ankylosing spondylitis (AS) and the relation between VF, measures of disease activity, and bone mineral density (BMD) in different measurement sites.

    METHODS: Patients with AS (modified New York criteria) underwent examination, answered questionnaires, and gave blood samples. Lateral spine radiographs were scored for VF (Genant score) and syndesmophyte formation through modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). BMD was measured with dual-energy x-ray absorptiometry in the hip, radius, and lumbar spine in anteroposterior and lateral projections with estimation of volumetric BMD (vBMD).

    RESULTS: Two hundred four patients (57% men) with a mean age of 50 ± 13 years and disease duration 15 ± 11 years were included. VF were diagnosed in 24 patients (12%), but were previously noted clinically in only 3 of the 24. Patients with VF were significantly older (p = 0.004), had longer disease duration (p = 0.011), higher Bath Ankylosing Spondylitis Metrology Index (p = 0.011), mSASSS (p = 0.035), and Bath Ankylosing Spondylitis patient global score-2 (BASG-2) (p = 0.032) and were more often smokers (p = 0.032). All women with a VF were postmenopausal. BMD was significantly lower at all measuring sites in the patients with VF. In logistic regression, high BASG-2, low BMD in femoral neck, and low lumbar vBMD were independently associated with presence of VF.

    CONCLUSION: VF in AS are common but are often not diagnosed. VF are associated with advanced age, longstanding disease, impaired back mobility, syndesmophyte formation, and lower BMD in both the central and peripheral skeleton. BMD in the femoral neck, total hip, and estimated vBMD showed the strongest association with VF.

  • 19. Klingberg, Eva
    et al.
    Nurkkala, Merja
    Carlsten, Hans
    Forsblad-d'Elia, Helena
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Biomarkers of bone metabolism in ankylosing spondylitis in relation to osteoproliferation and osteoporosis2014In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 41, no 7, p. 1349-56Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To identify biomarkers for bone metabolism in patients with ankylosing spondylitis (AS) and to determine the relationship between these biomarkers and disease activity, back mobility, osteoproliferation, and bone mineral density (BMD).

    METHODS: Serum levels of Wingless protein (Wnt-3a), Dickkopf-1 (DKK-1), sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), and osteoprotegerin were assessed using ELISA. Ankylosing Spondylitis Disease Activity Score-C reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis patient global score, and C-reactive protein (CRP) were used as disease activity measures, and Bath Ankylosing Spondylitis Metrology Index (BASMI) as a measure of spinal mobility. Lateral spine radiographs were scored for chronic AS-related changes (mSASSS). BMD was measured with dual-energy x-ray absorptiometry.

    RESULTS: Two hundred four patients with AS (NY criteria; 57% men), with a mean age of 50 ± 13 years and disease duration 15 ± 11 years, and 80 age and sex-matched controls were included. The patients with AS had significantly higher serum levels of Wnt-3a (p < 0.001) and lower levels of sclerostin (p = 0.014) and sRANKL (p = 0.047) compared with the controls. High CRP was associated with low sclerostin (r(S) = -0.21, p = 0.003) and DKK-1 (r(S) = -0.14, p = 0.045). In multiple linear regression analyses, increasing BASMI and mSASSS were independently associated with older age, male sex, high CRP, and elevated serum levels of Wnt-3a. In addition, mSASSS remained associated with a high number of smoking pack-years after adjusting for age. Low BMD of femoral neck was associated with high mSASSS after adjusting for age.

    CONCLUSION: Serum levels of Wnt-3a are elevated in AS and associated with increased BASMI and mSASSS, independent of age, indicating that Wnt-3a could be a biomarker for the osteoproliferative process.

  • 20.
    Lammi, Mikko
    et al.
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Qu, Cheng-Juan
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Laasanen, Mikko
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Saarakkala, Simo
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Rieppo, Jarno
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Töyräs, Juha
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Undersulfated chondroitin sulfate does not increase in osteoarthritic cartilage.2004In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 31, no 12, p. 2449-2453, article id 15570650Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To test whether there is undersulfation of chondroitin sulfate in osteoarthritic bovine articular cartilage to support the hypothesis that sulfate deficiency is involved with the development of osteoarthritis.

    METHODS: Cartilage samples from bovine patellae (n = 32) were divided into 3 groups based on their osteoarthritic progression, as assessed by modified Mankin score. Uronic acid contents of the samples were determined. Fragmentation of the proteoglycans due to proteolytic processing was estimated with agarose gel electrophoresis. The molar ratios of chondroitin sulfate isoforms in the extracted proteoglycans were determined with fluorophore-assisted carbohydrate electrophoresis.

    RESULTS: Loss of proteoglycans and accumulation of tissue water was evident in groups II and III, and progressive OA increased heterogeneity of aggrecan population in groups II and III. Importantly, the molar ratio of nonsulfated disaccharide was decreased in the osteoarthritic articular cartilage.

    CONCLUSION: The structure of chondroitin sulfate in degenerated bovine cartilage did not support the hypothesis that sulfate depletion is present in osteoarthritic joint.

  • 21. Lindqvist, Ulla R C
    et al.
    Alenius, Gerd-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Husmark, Tomas
    Theander, Elke
    Holmström, Gunilla
    Larsson, Per T
    The Swedish early psoriatic arthritis register-- 2-year followup: a comparison with early rheumatoid arthritis.2008In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 35, no 4, p. 668-73Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE :Patients with symptoms and signs compatible with psoriatic arthritis (PsA), with or without psoriasis, have been documented in the Swedish Early Psoriatic Arthritis (SwePsA) register. Our aim was to find markers for disease progression and to evaluate treatments for PsA using these data. METHODS: Patients referred to rheumatology outpatient clinics within 2 years of onset were assessed on inclusion and at followup 2 years later. Data collection was performed according to the program for SwePsA, and classification was as described by Moll and Wright and the ClASsification Criteria for Psoriatic ARthritis (CASPAR). Remission was recorded if the patient had no tender or swollen joints and if erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were within the reference range. Patients with early rheumatoid arthritis (RA) recruited from the Swedish Early Rheumatoid Arthritis Register (Ramona) provided comparison data. RESULTS: One hundred thirty-five patients with PsA according to CASPAR were assessed; 44% were classified as having mono/oligoarthritis and 47% as polyarthritis. Two patients (1%) were in remission initially, and 23 (17%) at followup. Patients with polyarticular disease had the highest inflammatory activity, measured by swollen and tender joint counts, ESR, Health Assessment Questionnaire, and self-assessment by visual analog scale of pain and global disease activity. Dactylitis was associated with radiological findings. Compared with RA patients, they had significantly lower CRP, ESR, and number of swollen joints (p = 0.0003, p = 0.0026, p = 0.0380, respectively) at inclusion, but equal numbers of tender joints and self-assessment of pain and disease activity. CONCLUSION: About half the patients had polyarthritis and the other half had mono/oligoarthritis at followup after 2 years. Patients with polyarthritis had the highest inflammatory activity. Apart from ESR, CRP, and swollen joint count, there were no significant differences in activity between RA and polyarticular PsA.

  • 22.
    Ljung, Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.
    Cardiovascular events in early rheumatoid arthritis: role of tumor necrosis factor inhibition2014In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 41, no 11, p. 2094-2096Article in journal (Other academic)
  • 23.
    Ljung, Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Karolinska Institutet, Department of Medicine Solna, Clinical Epidemiology Division, Stockholm.
    Holmqvist, Marie
    Methotrexate in Our Hearts2019In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 46, no 5, p. 447-449Article in journal (Other academic)
  • 24. Maksymowych, WP
    et al.
    Wessler, A
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Suarez-Almazor, M
    Ritzel, G
    Von Borstel, RC
    Pazderka, F
    Russell, AS
    Polymorphism in an HLA linked proteasome gene influences phenotypic expression of disease in HLA-B27 positive individuals1994In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 21, no 4, p. 665-669Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the potential influence of the HLA-linked LMP (low molecular weight polypeptide) genes on disease susceptibility in HLA-B27 individuals with ankylosing spondylitis (AS).

    METHODS: A polymorphic CfoI restriction enzyme site in the coding region of one proteasome gene was evaluated in 125 genomic DNA samples from B27 individuals with well documented AS, 55 of whom had had acute iritis, and 42 samples from normal, ethnically matched B27 blood donors where AS was excluded.

    RESULTS: Analysis of individuals with B27 AS with iritis revealed significant differences in allelic distribution of this biallelic locus compared to patients with B27 AS without iritis. Furthermore, homozygosity for the disease associated allele was significantly more prevalent in patients with AS with iritis (72.7%) than in patients without iritis (38.6%) (p(uncorrected) = 0.0003) or B27 controls (45.2%) (p(uncorrected) = 0.01).

    CONCLUSION: Our findings support the involvement of additional HLA linked genes in the phenotypic expression of disease in B27 individuals and suggest a role for the non-B27 HLA haplotype in susceptibility to iritis.

  • 25.
    Mäkelä, Olli
    et al.
    Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Uusitalo, Hannele
    Department of Medical Biochemistry and Molecular Biology, University of Turku, Turku, Finland.
    Viitanen, Minna
    Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
    Hyttinen, Mika
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Vuorio, Eero
    Department of Medical Biochemistry and Molecular Biology, University of Turku, Turku, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tulamo, Riitta-Mari
    Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
    Effect of radiosynovectomy with holmium-166 ferric hydroxide macroaggregate on adult equine cartilage.2004In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 31, no 2, p. 321-328, article id 14760804Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To analyze the effect of radiosynovectomy with holmium-166 ferric hydroxide macroaggregate (166Ho-FHMA) on articular cartilage in 6 adult horses.

    METHODS: Arthritic changes and mechanical properties of articular cartilage were evaluated with arthroscopy and postmortem microscopic analyses. Glycosaminoglycan content was measured by safranin-O staining combined with digital densitometry, uronic acid analyses, and dimethylene blue binding assay. 35S-sulfate labeling and autoradiography were used to localize proteoglycan synthesis and to characterize proteoglycan structures using SDS-agarose gel electrophoresis. Northern hybridizations were performed to measure the mRNA levels for aggrecan and pro-a1(II) collagen in cartilage samples.

    RESULTS: Histological signs of degeneration were present in the articular cartilage of both control and radiosynovectomized equine joints. Radiosynovectomy did not aggravate degenerative changes or significantly alter the matrix glycosaminoglycan content. A slightly decreased size of proteoglycan monomers was observed 2 months after 166Ho-FHMA radiosynovectomy. Tissue analysis of extracted proteoglycans revealed lower 35S incorporation after radiosynovectomy, but corresponding changes could not be observed in aggrecan mRNA levels. Transient downregulation of pro-a1(II) collagen mRNA transcription was observed 5 days after 166Ho-FHMA radiosynovectomy.

    CONCLUSION: 166Ho-FHMA treatment did not markedly affect the composition or morphology of adult articular cartilage showing mild degeneration. However, minor degradation of proteoglycan monomers and transient downregulation of pro-a1(II) collagen mRNA were observed.

  • 26. Nordström, Dan
    et al.
    Knight, Ann
    Luukkainen, Reijo
    van Vollenhoven, Ronald
    Rantalaiho, Vappu
    Kajalainen, Anna
    Brun, Johan G
    Proven, Anne
    Ljung, Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Kautiainen, Hannu
    Pettersson, Tom
    Beneficial Effect of Interleukin 1 Inhibition with Anakinra in Adult-onset Still's Disease. An Open, Randomized, Multicenter Study2012In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 39, no 10, p. 2008-2011Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the efficacy of anakinra versus disease-modifying antirheumatic drugs (DMARD) in refractory adult-onset Still's disease (AOSD). METHODS: In a 24-week study, 22 patients with AOSD taking prednisolone ≥ 10 mg/day received anakinra (n = 12) or DMARD (n = 10). The primary endpoint was achievement of remission. RESULTS: At 8 and 24 weeks, 7/12 and 6/12 receiving anakinra and 5/10 and 2/10 receiving DMARD achieved remission. Anakinra induced greater improvement in physical health measured by Medical Outcomes Study Short-Form 36 (SF-36; p < 0.011). During an open-label extension (OLE) of 28 weeks, 7/14 patients taking anakinra and 2/3 taking DMARD were in remission. CONCLUSION: Anakinra induced more beneficial responses than DMARD in patients with AOSD and was favored in the OLE phase. (ClinicalTrials.gov Protocol Registration NCT01033656).

  • 27. Pullerits, Rille
    et al.
    Urbonaviciute, Vilma
    Voll, Reinhard E
    Forsblad-D'Elia, Helena
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Carlsten, Hans
    Serum levels of HMGB1 in postmenopausal patients with rheumatoid arthritis: associations with proinflammatory cytokines, acute-phase reactants, and clinical disease characteristics.2011In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 38, no 7, p. 1523-5Article in journal (Refereed)
  • 28.
    Sundström, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Johansson, Gunnar
    School of social and health sciences, Halmstad university, Halmstad, Sweden.
    Kokkonen, Heidi
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Cederholm, Tommy
    Division of clinical nutrition and metabolism, department of public health and caring science, Uppsala university, Uppsala, Sweden.
    Wållberg-Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Plasma phospholipid fatty acid content is related to disease activity in ankylosing spondylitis2012In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 39, no 2, p. 327-333Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate the fatty acid composition in the diet, plasma phospholipids, and adipose tissue among a cohort of patients with ankylosing spondylitis (AS), and to determine their correlation to disease activity and blood lipids in a cross-sectionally designed study.

    Methods: Diet was assessed using a food frequency questionnaire on 66 patients with AS. The polyunsaturated fatty acids (PUFAs) in plasma phospholipids and gluteal adipose tissue were measured using gas chromatography. Disease status was quantified using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein and pro-inflammatory cytokines.

    Results: Diet did not correlate to disease activity assessed by the BASDAI, but there were negative correlation between the dietary intake of long-chained omega-3 fatty acids and ESR (rs=-0.27, p<0.05). The plasma phospholipid content of arachidonic acid (AA) correlated significantly with the BASDAI score (rs=0.39, p<0.01). There were correlations between the intake of long-chained omega-3 fatty acids and high-density lipoproteins as well as to serum triglycerides (rs=0.26 and rs=-0.25; respectively, p<0.05).

    Conclusion: There was a positive correlation between levels of AA in plasma phospholipids and disease activity assessed by BASDAI in patients with AS. A western diet does not appear to influence this correlation, but seems to affect blood lipids involved in atherogenic processes. 

  • 29.
    Södergren, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Karp, Kjell
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Bengtsson, Christine
    Moller, Bozena
    Rantapää-Dahlqvist, Solbritt
    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.
    The Extent of Subclinical Atherosclerosis Is Partially Predicted by the Inflammatory Load: A Prospective Study over 5 Years in Patients with Rheumatoid Arthritis and Matched Controls2015In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 6, p. 935-942Article in journal (Refereed)
    Abstract [en]

    Objective. This prospective followup study investigated subclinical atherosclerosis in relation to traditional cardiovascular disease (CVD) risk factors and inflammation in patients with rheumatoid arthritis (RA) recruited at diagnosis compared with controls. Methods. Patients diagnosed with early RA were consecutively recruited into a prospective study. From these, a subgroup aged <= 60 years (n = 71) was consecutively included for ultrasound measurement of intima-media thickness (IMT) and flow-mediated dilation (FMD) at inclusion (T0) and after 5 years (T5). Age-and sex-matched controls (n = 40) were also included. Results. In the Wilcoxon signed-rank test, both IMT and FMD were significantly aggravated at T5 compared to baseline in patients with RA, whereas only IMT was significantly increased in controls. In univariate linear regression analyses among patients with RA, the IMT at T5 was significantly associated with age, systolic blood pressure (BP), cholesterol, triglycerides, Systematic Coronary Risk Evaluation (SCORE), and Reynolds Risk Score at baseline (p < 0.05). Similarly, FMD at T5 was significantly inversely associated with age, smoking, systolic BP, SCORE, and Reynolds Risk Score (p < 0.05). A model with standardized predictive value from multiple linear regression models including age, smoking, BP, and blood lipids at baseline significantly predicted the observed value of IMT after 5 years. When also including the area under the curve for the 28-joint Disease Activity Score over 5 years, the observed value of IMT was predicted to a large extent. Conclusion. This prospective study identified an increased subclinical atherosclerosis in patients with RA. In the patients with RA, several traditional CVD risk factors at baseline significantly predicted the extent of subclinical atherosclerosis 5 years later. The inflammatory load over time augmented this prediction.

  • 30. Uddhammar, A
    et al.
    Rantapää-Dahlqvist, Solbritt
    Thornell, L E
    Polymyalgia rheumatica, aging, and mitochondria - Reply1999In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 26Article in journal (Refereed)
  • 31. Uddhammar, Agneta
    et al.
    Eriksson, Anna-Lena
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Increased mortality due to cardiovascular disease in patients with giant cell arteritis in Northern Sweden2002In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 29, no 4, p. 737-742Article in journal (Refereed)
    Abstract [en]

    Objective. To study the cause of death pattern in patients with giant cell arteritis (GCA) or polymyalgia rheumatica (PMR). and to analyze the effect of the disease, or its therapy, on the risk of a cardiovascular event (CVE).

    Methods. Patients with biopsy proven GCA or with PMR, whose condition was diagnosed between 1973 and 1979, were followed until December 31, 1995. The standardized mortality ratio (SMR) was estimated using data for the population of V sterbotten, Northern Sweden, as reference value. Information for sex, age at diagnosis, erythrocyte sedimentation rate (ESR) at diagnosis, corticosteroid therapy, comorbidity from diagnosis, and date and cause of death was collected.

    Results. A total of 136 patients with GCA and 35 with PMR were identified. At the time of followup 114 patients with GCA and 25 with PMR were deceased. The overall mortality was significantly increased in the female patients, SMR = 133 (95% Cl 110-162). Death due to cardiovascular disease (CVD) was significantly increased in both women and men, SMR = 149 (95% CI 118-189) and 158 (95% Cl 112-224), respectively, and mainly due to ischemic heart disease. An excess mortality was found in women with the hi-hest ESR, the highest prescribed dose of prednisolone at diagnosis, or a daily prednisolone dose of 10 mg or more one year after diagnosis. In multiple Cox regression analysis, male sex and hypertension significantly increased the risk of a CVE.

    Conclusion. Death due to CVD was increased in patients with GCA. Increased mortality was related to either the corticosteroid therapy itself or insufficient control of inflammation.

  • 32.
    Wahlin, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Innala, Lena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Magnusson, Staffan
    Möller, Bozena
    Smedby, Torgny
    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.
    Performance of the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis Is Not Superior to the ACC/AHA Risk Calculator2019In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, p. 130-137Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cardiovascular (CV) risk estimation calculators for the general population do not perform well in patients with rheumatoid arthritis (RA). An RA-specific risk calculator has been developed, but did not perform better than a risk calculator for the general population when validated in a heterogeneous multinational cohort.

    METHODS: In a cohort of patients with new-onset RA from northern Sweden (n = 665), the risk of CV disease was estimated by the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA) and the American College of Cardiology/American Heart Association algorithm (ACC/AHA). The ACC/AHA estimation was analyzed, both as crude data and when adjusted according to the recommendations by the European League Against Rheumatism (ACC/AHA × 1.5). ERS-RA was calculated using 2 variants: 1 from patient and physician reports of hypertension (HTN) and hyperlipidemia [ERS-RA (reported)] and 1 from assessments of blood pressure (BP) and blood lipids [ERS-RA (measured)]. The estimations were compared with observed CV events.

    RESULTS: All variants of risk calculators underestimated the CV risk. Discrimination was good for all risk calculators studied. Performance of all risk calculators was poorer in patients with a high grade of inflammation, whereas ACC/AHA × 1.5 performed best in the high-inflammatory patients. In those patients with an estimated risk of 5-15%, no risk calculator performed well.

    CONCLUSION: ERS-RA underestimated the risk of a CV event in our cohort of patients, especially when risk estimations were based on patient or physician reports of HTN and hyperlipidemia instead of assessment of BP and blood lipids. The performance of ERS-RA was no better than that of ACC/AHA × 1.5, and neither performed well in high-inflammatory patients.

  • 33. Wallberg-Jonsson, S
    et al.
    Rantapää-Dahlqvist, Solbritt
    Ohman, M L
    Risk of cardiovascular events and effect on mortality in patients with rheumatoid arthritis - Reply2000In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 27, p. 2282-2283Article in journal (Refereed)
  • 34. Wang, Chuan
    et al.
    Kokkonen, Heidi
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Sandling, Johanna K
    Johansson, Martin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Seddighzadeh, Maria
    Padyukov, Leonid
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Syvänen, Ann-Christine
    Preferential association of interferon regulatory factor 5 gene variants with seronegative rheumatoid arthritis in 2 Swedish case-control studies2011In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 38, no 10, p. 2130-2132Article in journal (Refereed)
    Abstract [en]

    Objective: Two interferon regulatory factor 5 (IRF5) gene variants were examined for association with rheumatoid arthritis (RA).

    Methods: A total of 2300 patients with RA and 1836 controls were recruited from 2 independent RA studies in Sweden. One insertion-deletion polymorphism (CGGGG indel) and one single-nucleotide polymorphism (rs10488631) in the IRF5gene were genotyped and analyzed within RA subgroups stratified by rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA).

    Results: The CGGGG indel was preferentially associated with the RF-negative (OR 1.29, p = 7.9 × 10−5) and ACPA-negative (OR 1.27, p = 7.3 × 10−5) RA subgroups compared to the seropositive counterparts. rs10488631 was exclusively associated within the seronegative RA subgroups (RF-negative: OR 1.24, p = 0.016; ACPA-negative: OR 1.27, p = 4.1 × 10−3).

    Conclusion: Both the CGGGG indel and rs10488631 are relevant for RA susceptibility, especially for seronegative RA.

  • 35.
    Wang, Weizhuo
    et al.
    Department of Orthopedic Surgery, Second Hospital of Xi’an Jiaotong University, Xi'an, China.
    Guo, Xiong
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Xi'an, China.
    Chen, Junchang
    Department of Orthopedic Surgery, Second Hospital of Xi’an Jiaotong University, Xi'an, China.
    Xu, Peng
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Xi'an, China.
    Lammi, Mikko
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Morphology and phenotype expression of types I, II, III, and X collagen and MMP-13 of chondrocytes cultured from articular cartilage of Kashin-Beck Disease.2008In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, ISSN 0315-162X (Print), 1499-2752 (Online), Vol. 35, no 4, p. 696-702, article id 18322983Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We investigated the characteristics of cell morphology and expression of types I, II, III, and X collagen and matrix metalloproteinase-13 (MMP-13) of chondrocytes from articular cartilage of adult patients with Kashin-Beck Disease (KBD) in vitro to understand the pathogenesis in chondrocytes.

    METHODS: Samples of articular cartilage were divided into 2 groups: KBD group (8 samples, 8 cases) and the control (8 samples, 8 cases). KBD patients were diagnosed according to "Pathological Criteria to Diagnose KBD in China." Hyaline cartilage was digested with collagenase into cell suspensions and cultured in monolayers. Chondrocyte ultrastructure was observed by electron microscope at 10th day in vitro. Primary articular chondrocytes were seeded on microscope slides and immunostained on 12th day of cultivation for types I, II, III, and X collagens and MMP-13. Positive findings were counted by light microscopy and confirmed by flow cytometric analyses.

    RESULTS: Considerable amounts of vacuoles and distorted nuclei, as well as thickening and irregular arrangement of collagen fibrils, were seen in the KBD samples by electron microscopy. Types I, III, and X collagen were stained in the KBD, but not in the control cultures. The percentages of positive staining for type II collagen were significantly lower in KBD than those in controls (t col II = -5.54, p < 0.001), and for MMP-13 in the KBD group were significantly higher (t MMP-13 = 3.70, p < 0.01).

    CONCLUSION: Phenotype expressions of types I, II, III, and X collagen and MMP-13 in chondrocytes cultured in vitro were significantly different between the KBD and control cultures, indicating degenerative and hypertrophic changes in chondrocytes of KBD articular cartilage.

  • 36.
    Wållberg-Jonsson, Solveig
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cederfelt, M
    Dahlqvist, Solbritt Rantapää
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Hemostatic factors and cardiovascular disease in active rheumatoid arthritis: an 8 year followup study2000In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 27, no 1, p. 71-75Article in journal (Refereed)
    Abstract [en]

    Objective. To investigate the prospective effect of hemostatic factors and inflammatory variables on the progression of cardiovascular disease in rheumatoid arthritis (RA).

    Methods. Von Willebrand factor (vWF) and the fibrinolytic factors tissue plasminogen activator (tPA), measured as tPA capacity, and plasminogen activator inhibitor 1 (PAI-1), platelets, fibrinogen, and inflammatory markers were measured in 74 patients with active seropositive RA. Lipid levels, lipoprotein(a), and cardiolipin antibodies were also analyzed. Cardiovascular disease, measured by past cardiovascular events including thrombotic events, was registered in an 8 year followup.

    Results. Patients with a cardiovascular event during the followup period (n = 26) had significantly higher levels of vWF PAI-1, erythrocyte sedimentation rate (ESR), and haptoglobin at entry to the study. In a multiple logistic regression model controlling for several conventional cardiovascular risk factors and pharmacological treatment at sampling, PAI-1 and tPA were significantly associated with cardiovascular disease progression.

    Conclusion. The altered levels of vWF, PAI-1, and, in logistic regression, tPA in RA patients with cardiovascular disease progression indicates a status of hypofibrinolysis in these patients. Higher levels of ESR and haptoglobin may reflect the importance of the inflammatory process for the development of cardiovascular disease in RA.

  • 37.
    Wållberg-Jonsson, Solveig
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Johansson, Helene
    Öhman, Marie-Louise
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis: A retrospective cohort study from disease onset1999In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 26, no 12, p. 2562-2571Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To identify predictors for cardiovascular disease (CVD) and for overall survival in patients with rheumatoid arthritis (RA) followed from disease onset.

    METHODS: A retrospective cohort of patients with seropositive RA and disease onset between 1974 and 1978 (n = 211) was followed up at the end of 1995. Potential predictors for CVD, as measured by "the first cardiovascular event," and for overall survival were registered. The predictors were identified by extended Cox regression models.

    RESULTS: In simple Cox regression analysis, male sex, higher age at disease onset, HLA-B27, high disease activity, corticosteroid treatment early in disease, and hypertension significantly increased risk of cardiovascular event. Higher educational level, extensive disease modifying antirheumatic drug (DMARD) treatment, and corticosteroids > or =1 yr before event decreased the risk. In multiple Cox regression analysis, male sex, high age at disease onset, hypertension, higher haptoglobin level at disease onset, and corticosteroid treatment early in disease increased risk of CVD. In a multiple model comprising only patients with CVD, corticosteroids delayed the event. A high last registered erythrocyte sedimentation rate (ESR) value before event increased CVD risk, in particular when early in disease progression. Decreased life span was predicted by higher age at disease onset, male sex, low education level, high disease activity, hypertension, and CVD. HLA-B27 was associated with decreased life span, as was early, but not extensive corticosteroid treatment. DMARD treatment was associated with decreased mortality risk, as was the presence of joint prosthesis. In multiple regression, male sex, higher age at disease onset, atlantoaxial subluxation early in disease, hypertension, and cardiovascular event increased mortality. A high last registered ESR value before event or death added to that risk.

    CONCLUSION: The study emphasizes the importance of inflammation as an important risk indicator for CVD and mortality in RA. The positive impact of disease activity reducing treatment on CVD risk and survival is suggested.

  • 38.
    Wållberg-Jonsson, Solveig
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Öhman, Marie-Louise
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden.1997In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 24, no 3, p. 445-451Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the overall and the cardiovascular mortality in rheumatoid arthritis (RA) in Northern Sweden. To analyze the effect of traditional risk factors and factors associated with rheumatoid disease and its treatment on the progression of cardiovascular disease (CVD) and on mortality by all causes. METHODS: A cohort of 606 patients with seropositive RA were followed from 1979 to the end of 1994 or to the death of the patient. Standardized mortality ratio and survival curves were estimated with the population of Vasterbotten as reference. Sex, age at disease onset, treatment with corticosteroids, use of disease modifying antirheumatic drugs (DMARD) and hormone replacement therapy (HRT), hypertension, diabetes mellitus, HLA types, and cause of death were recorded from disease onset. Cox's proportional hazards regression was used to identify important predictors for death and cardiovascular event during followup. RESULTS: The standardized mortality ratio in both sexes was significantly higher (1.57) for all underlying causes together, for CVD (1.46) and for ischemic heart disease (IHD) (1.54) compared to the reference population. The death rate increased over time. In multiple Cox regression analyses, male sex, higher age at disease onset, and former cardiovascular event increased the death rate. Male sex, high age at disease onset, and hypertension increased the risk of cardiovascular event. Diabetes mellitus, treatment with corticosteroids, DMARD, or HRT did not influence the risks of death or first cardiovascular event. CONCLUSION: The overall mortality and death due to CVD and IHD were in both sexes increased in seropositive RA. Male sex and high age at disease onset predicted death and cardiovascular event. Except for hypertension, which increased the risk for cardiovascular event, neither of these traditional cardiovascular risk factors nor corticosteroid treatment influenced mortality by all causes or by cardiovascular event.

  • 39.
    Ärlestig, Lisbeth
    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.
    Polymorphisms of the Genes Encoding CD40 and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease2012In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 39, no 5, p. 939-945Article in journal (Refereed)
    Abstract [en]

    Objective. Genes or gene products associated with coronary artery disease in the general population were analyzed in rheumatoid arthritis (RA) patients with atherothrombotic manifestations (ATM). Methods. A cross-sectional study of 681 individuals (498 women; 183 men) with RA (American College of Rheumatology criteria), a mean age of 60.6 +/- 13.2 years, and mean disease duration of 15.5 +/- 12.6 years who were consecutively recruited and followed for 6 years. The prevalence of ATM [i.e., myocardial infarction, angina pectoris with intervention, deep vein thrombosis/pulmonary embolism (DVT/PE), and/or stroke/transient ischemic attack (TIA)] was recorded. Polymorphisms were analyzed in the genes coding for growth differentiation factor 15 (GDF15)/monocyte inhibitory cytokine-1 (MIC-1; rs1058587), CD40 (rs1535045 and rs3765459), and the 9p21.3 locus (rs1333049). Controls were randomly selected (n = 687; matched for age and sex). Results. The distribution of genotypes of GDF15/MIC-1 differed significantly between patients with RA and controls (chi-squared = 6.40, 2 df, p = 0.041). ATM were associated with polymorphism of the GDF15/MIC-1 G allele (OR 2.21, 95% CI 1.17-4.18), and with CC genotype of the 9p21.3 locus (rs1333049; OR 1.92, 95% CI 1.15-3.19). Stroke/TIA in women was associated with GDF15/MIC-1 GG genotype (OR 3.75, 95% CI 1.06-13.33), while stroke/TIA in men was associated with CD40 homozygous major alleles (OR 6.48, 95% CI 1.31-32.0 and OR 2.78,95% CI 0.78-9.91, respectively). DVT/PE was associated with polymorphism in the GDF15/MIC-1 gene (rs1058587) minor allele (OR 3.53, 95% CI 1.30-9.58). Conclusion. The gene polymorphisms analyzed were associated with different ATM in RA. The GDF15/MIC-1 gene polymorphism was also associated with RA per se, suggesting a common etiology for RA and ATM. (First Release April 15 2012; J Rheumatol 2012;39:939-45; doi:10.3899/jrheuin.111336)

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