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- Lundberg, Karin, et al.
(author)
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Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defined by the anticitrullinated protein/peptide antibody fine specificity profile
- 2013
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In: Annals of the Rheumatic Diseases. - Stockholm : Karolinska Institutet, Dept of Medicine, Solna. - 1468-2060 .- 0003-4967.
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To increase understanding of the aetiology and pathogenesis of rheumatoid arthritis (RA), genetic and environmental risk factors for RA subsets, defined by the presence or absence of different anticitrullinated protein/peptide antibodies (ACPAs) targeting citrullinated peptides from α-enolase, vimentin, fibrinogen and collagen type II, were investigated. METHODS: 1985 patients with RA and 2252 matched controls from the EIRA case-control cohort were used in the study. Serum samples were assayed by ELISA for the presence of anticyclic citrullinated peptides (anti-CCP) antibodies and four different ACPA fine specificities. Cross-reactivity between ACPAs was examined by peptide absorption experiments. Genotyping was performed for HLA-DRB1 shared epitope (SE) alleles and the PTPN22 gene, while information regarding smoking was obtained by questionnaire. The association of genetic and environmental risk factors with different subsets of RA was calculated by logistic regression analysis. RESULTS: Limited cross-reactivity was observed between different ACPA fine specificities. In total, 17 RA subsets could be identified based on their different ACPA fine specificity profiles. Large differences in association with genetic and environmental determinants were observed between subsets. The strongest association of HLA-DRB1 SE, PTPN22 and smoking was identified for the RA subset which was defined by the presence of antibodies to citrullinated α-enolase and vimentin. CONCLUSION: This study provides the most comprehensive picture to date of how HLA-DRB1 SE, PTPN22 and smoking are associated with the presence of specific ACPA reactivities rather than anti-CCP levels. The new data will form a basis for molecular studies aimed at understanding disease development in serologically distinct subsets of RA.
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- Agmon-Levin, Nancy, et al.
(author)
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International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies
- 2014
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 73:1, s. 17-23
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Journal article (peer-reviewed)abstract
- 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.
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- Ahlmen, M, et al.
(author)
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Influence of gender on assessments of disease activity and function in early rheumatoid arthritis in relation to radiographic joint damage
- 2010
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:1, s. 230-233
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Journal article (peer-reviewed)abstract
- To evaluate gender differences in score on 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) and Signals Of Functional Impairment (SOFI) and to relate these scores to radiographic joint destruction.Methods:In all, 549 patients with early RA (62% women) from the BARFOT (for “Better Anti-Rheumatic FarmacOTherapy”) study were included. At baseline, 1, 2 and 5 years DAS28, HAQ and SOFI scoring, and radiographs of hands and feet were performed. The radiographs were scored using the van der Heijde–Sharp score.Results:In women the DAS28 was significantly higher than in men due to higher scores for general health and tender joints. Likewise, HAQ and VAS pain were rated significantly higher in women. The SOFI score was worse in men during the first 2 years, depending on higher upper limb scores. Total Sharp score (TotSharp), erosion score and joint space narrowing score did not differ between the sexes at any time point. The DAS28 area under the curve (AUC) correlated significantly with TotSharp at 5 years in both genders (r = 0.316, r = 0.313) mainly owing to swollen joints and erythrocyte sedimentation rate (ESR). The SOFI AUC correlated significantly with TotSharp in women (r = 0.135 to 0.220) but not in men.Conclusions:Despite a similar degree of radiographic joint destruction women had, compared with men, worse scores for DAS28 and HAQ, possibly due to higher pain perception and less muscular strength and perhaps because men overestimate their functional capacity.
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- Ahlstrand, Inger, et al.
(author)
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Less pain and activity limitations in today's early RA patients compared with patients diagnosed 10 years earlier (the swedish TIRA-project)
- 2014
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In: EULAR 2014: Scientific Abstracts. - : BMJ. ; , s. 141-142
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Conference paper (peer-reviewed)abstract
- Background: Over the last decades the RA-treatment strategies have changed considerably. Routines for early RA diagnosis and instituted disease modifying anti rheumatic drugs (DMARDs) have been established. In the early 2000s biologic agents also became available for treatment purposes. Despite these altered and improved strategies RA patients continue to report pain and activity limitations; women more so than men.Objectives: To study differences regarding pain and activity limitations during the first three years after diagnosis of RA in today's patients compared with patients diagnosed 10 years earlier from a gender perspective.Methods: This study was based on patients recruited to the project “early interventions in RA” (TIRA). In the first cohort (TIRA-1) 320 patients were included during 1996-1998. In the second cohort (TIRA-2) 463 patients were included during 2006-2008. Disease activity score 28 joint count (DAS-28) and medication were registered. Pain intensity (VAS), bodily pain (BP) in Short Form36 (SF-36) and activity limitation (Health Assessment Questionnaire, HAQ) were reported at inclusion and at follow-ups after one, two and three years.Results: Disease activity did not differ between cohorts at inclusion, but was significant lower at the follow ups in the TIRA-2 cohort compared with the TIRA-1 cohort. Patients in TIRA2 were prescribed traditional DMARD:s and biologic agents more frequent than in TIRA-1. The TIRA-2 patients reported significantly higher pain intensity and activity limitations at inclusion but lower pain intensity and activity limitations at all follow-ups than TIRA-1 patients. There were no significant differences between cohorts regarding bodily pain at inclusion, but thereafter the TIRA-2 patients showed significant lower bodily pain than the TIRA-1 patients. Men reported lower activity limitation than women in TIRA-1; otherwise there were no gender differences in TIRA-1. In TIRA-2, there were no significant gender differences regarding pain at inclusion. However, men reported lower pain than women at all follow-ups. Women, in turn, reported significantly higher activity limitations at all time points in TIRA-2. Pain and activity limitations were significantly reduced from inclusion to the one year follow-up but remained stable thereafter.Conclusions: Both women and men in today's early RA patient cohort report lower pain and less activity limitations at the follow ups after diagnosis of RA compared to 10 years earlier. However, both activity limitations and bodily pain are still pronounced.
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