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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
  1. M Cornillet1,
  2. M Sebbag1,
  3. E Verrouil2,3,
  4. A Magyar4,
  5. A Ruyssen-Witrand2,
  6. F Hudecz4,
  7. A Cantagrel2,
  8. G Serre1,3,
  9. L Nogueira1,3
  1. 1Laboratory of “Epidermis Differentiation and Rheumatoid Autoimmunity”, UMR CNRS 5165, INSERM U 1056, Toulouse III University
  2. 2Rheumatology Center, University Hospital of Toulouse
  3. 3Laboratory of Cell Biology and Cytology, University Hospital of Toulouse; Toulouse, France
  4. 4Research Group of Peptide Chemistry, Department of Organic Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Budapest, Hungary

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.

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