A5.7 Autoantibodies to the Fibrin-Derived Citrullinated Peptides α36–50 and β60–74 are Two Distinct Non-Overlapping Subfamilies of ACPA that together almost Summarise their Reactivity to Citrullinated Fibrinogen and to CCP2 Antigens. (25th February 2013)

• Record Type: Journal Article
• Authors: Cornillet, M; Sebbag, M; Verrouil, E; Magyar, A; Ruyssen-Witrand, A; Hudecz, F; Cantagrel, A; Serre, G; Nogueira, L
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Supplement 1(2013)
• Page Start: A32
• Page End: A32
• Publication Date: 2013-02-25
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-203219.7
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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.