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Background: The goal of our study was to evaluate the diagnostic performance of the anti-cyclic citrullinated peptide 2 (anti-CCP2) assay in patients with autoimmune and inflammatory disorders. Methods: We tested the specificity and sensitivity of anti-CCP2 antibodies measured by ELISA in 787 patients with rheumatoid arthritis (RA), 1024 patients with other autoimmune/inflammatory rheumatic disease and 401 subjects without autoimmune rheumatic disease. The optimal cut-off value was defined as the value with the highest diagnostic accuracy (receiver operating characteristic curve analysis). Interval-specific likelihood ratios (LRs) were calculated for each range bounded by defined anti-CCP2 values. Results: To distinguish between patients with RA and controls, the cut-off value with the highest diagnostic accuracy for anti-CCP2 was 2.8 U/mL. Comparing the optimal cut-off value for anti-CCP2 to that recommended by the manufacturer (5.0 U/mL), an increase in prevalence between the proportions of test-positive patients was found for RA, undifferentiated connective tissue disease and undifferentiated arthritis. Evaluating interval-specific LRs for the selected ranges bound by two anti-CCP2 values, in RA and diseased controls, the LRs were 0.40 for values <5.0 U/mL, 6.66 for 5.0–15.0 U/mL, 27.01 for 15.1–30.0 U/mL and 28.89 for >30.0 U/mL. Conclusions: The cut-off value of 2.8 U/mL for anti-CCP2 has the highest diagnostic accuracy. A value of anti-CCP2 >15 U/mL is associated with an increase in the likelihood of RA disease. Clin Chem Lab Med 2010;48:829–34. [ABSTRACT FROM AUTHOR]

Abstract: We analyzed peripheral blood (PB) and synovial fluid (SF) mononuclear cells from 16 rheumatoid arthritis (RA), 9 spondyloarthritis (SpA), 3 microcrystal arthritis patients, to define the presence of Th17 and Th1 and their relationship with inflammatory activity, and TCR-zeta chain and ZAP-70 levels. Th17 were significantly higher in SF than in PB and more abundant in microcrystal arthritis patients compared to the other groups. Irrespectively of the diagnosis, SF Th17 percentages correlated with joint (SF total leukocyte count, neutrophil percentage) and systemic (C reactive protein [CRP], fibrinogen, erythrocyte sedimentation rate) inflammation markers. SF Th1 percentages directly correlated with inflammation and disease activity (CRP, swollen joint count [SJC]) indices in SpA, but not in RA patients. These observations support the role of Th17 in the pathogenesis of inflammatory arthritides. The TCR-zetadim lymphocytes in SF were found to produce the highest amounts of cytokines including IL-17, whereas no ZAP-70 impairment was associated to Th17. [ABSTRACT FROM AUTHOR]