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The fibrin-derived citrullinated peptide β60–74Cit60,72,74 bears the major ACPA epitope recognised by the rheumatoid arthritis-specific anticitrullinated fibrinogen autoantibodies and anti-CCP2 antibodies
  1. M Cornillet1,
  2. M Sebbag1,
  3. E Verrouil2,3,
  4. A Magyar4,
  5. F Babos4,
  6. A Ruyssen-Witrand2,
  7. F Hudecz4,
  8. A Cantagrel2,
  9. G Serre1,3,
  10. L Nogueira1,3
  1. 1‘Epidermis Differentiation and Rheumatoid Autoimmunity’ Laboratory, UMR CNRS 5165, INSERM U 1056, Toulouse III University, Toulouse, France
  2. 2Rheumatology Centre, Toulouse University Hospital, Toulouse, France
  3. 3Cell Biology and Cytology Laboratory, Toulouse University Hospital, Toulouse, France
  4. 4Research Group of Peptide Chemistry, Department of Organic Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Budapest, Hungary
  1. Correspondence to Dr Leonor Nogueira, ‘Epidermis Differentiation and Rheumatoid Autoimmunity’ Laboratory, UMR 5165 CNRS—U 1056 INSERM—Toulouse III University and Cell Biology and Cytology Laboratory, Toulouse University Hospital, Toulouse, 31059, France; Nogueira.l{at}chu-toulouse.fr

Abstract

Objectives To evaluate the proportions of rheumatoid arthritis (RA) sera containing anticitrullinated proteins autoantibodies (ACPA) reactive to α36–50Cit38,42 and/or β60–74Cit60,72,74, two peptides identified as bearing the immunodominant epitopes of their major target, citrullinated fibrin. To analyse the relationships of anti-α36–50Cit38,42 and anti-β60–74Cit60,72,74 autoantibodies with autoantibodies reactive to the complete citrullinated human fibrinogen molecule (AhFibA) and with anti-CCP2 antibodies.

Methods  617 sera from 181 patients with established RA and 436 with non-RA rheumatic diseases were tested by ELISA for AhFibA, anti-CCP2, anti-α36–50Cit38,42, anti-β60–74Cit60,72,74 autoantibodies, and by nephelometry for rheumatoid factor (RF). Diagnostic indexes, correlations and concordances between tests were analysed. Crossreactivity of anti-α36–50Cit38,42 and anti-β60–74Cit60,72,74 autoantibodies was assessed in competition experiments.

Results At a diagnostic specificity of 95%, the diagnostic sensitivity of AhFibA (83%) was significantly higher than that of all other tests. The diagnostic sensitivity of anti-β60–74Cit60,72,74 (71%) was significantly higher than that of anti-α36–50Cit38,42 autoantibodies (51%) but similar to that of anti-CCP2 (74%). Titres of RF, anti-α36–50Cit38,42 and anti-β60–74Cit60,72,74 autoantibodies were weakly correlated with each other, whereas titres of anti-β60–74Cit60,72,74 were strongly correlated with those of AhFibA (r=0.633) and anti-CCP2 (r=0.634). Anti-α36–50Cit38,42 and anti-β60–74Cit60,72,74 mainly corresponded to two non-crossreactive subfamilies of ACPA. More than 90% of AhFibA-positive or anti-CCP2-positive sera recognised the α36–50Cit38,42 and/or the β60–74Cit60,72,74 peptide.

Conclusions Autoantibodies reactive to α36–50Cit38,42 and β60–74Cit60,72,74 form two distinct, non-overlapping subfamilies of ACPA that, together, cover practically all the ACPA reactivity to citrullinated fibrinogen and to CCP2 antigens. In established RA, anti-β60–74Cit60,72,74 autoantibodies show diagnostic indexes similar to those of anti-CCP2.

  • Ant-CCP
  • Autoantibodies
  • B cells
  • Rheumatoid Arthritis
  • Autoimmunity

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