Objectives To evaluate the proportions of Rheumatoid Arthritis (RA) sera containing autoantibodies to citrullinated proteins (ACPA) reactive to α36–50 and/or β60–74, two citrullinated peptides identified as bearing the immunodominant epitopes of their major target: citrullinated fibrin. To analyse the relationships of anti-α36–50 and anti-β60–74 autoantibodies with autoantibodies to the whole citrullinated human fibrinogen (AhFibA) and with anti-CCP2 antibodies.
Methods 617 sera from 181 established RA and 436 non-RA rheumatic diseases were tested by ELISA for AhFibA, anti-CCP2, anti-α36–50, anti-β60–74 autoantibodies, and by nephelometry for Rheumatoid Factor (RF). Diagnostic indexes, correlations and concordances between tests were analysed. Cross–reactivity between anti-α36–50 and anti-β60–74 autoantibodies was analysed with peptide absorption experiments.
Results At diagnostic specificity of 95%, the diagnostic sensitivity of AhFibA (83%) was significantly higher than that of all other tests. The diagnostic sensitivity of anti-β60–74 autoantibodies (71%) was significantly higher than that of anti-α36–50 (51%) but similar to that of anti-CCP2 (74%). Titres of RF, anti-α36–50 and anti-β60–74 autoantibodies were weakly correlated with each other, whereas titres of anti-β60–74 were strongly correlated with those of AhFibA (rho = 0.633) and of anti-CCP2 (rho = 0.634). More than 90% of AhFibA-positive or anti-CCP2-positive sera recognised the α36–50 and/or the β60–74 peptide. Absorption experiments showed that anti-α36–50 and anti-β60–74 mainly correspond to 2 non-cross reactive subfamilies of ACPA.
Conclusions Autoantibodies to α36–50 and β60–74 are two distinct non-overlapping subfamilies of ACPA that together almost summarise the ACPA reactivity to citrullinated fibrinogen and to CCP2 antigens. In established RA, anti-β60–74 autoantibodies show diagnostic indexes similar to those of anti-CCP2.
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