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

M. Cornillet, M. Sebbag, E. Verrouil, A. Magyar, F. Babos, A. Ruyssen-Witrand, F. Hudecz, A. Cantagrel, G. Serre, L. Nogueira

Research output: Contribution to journalArticle

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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- 50Cit 38,42, 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 noncrossreactive 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.

Original languageEnglish
Pages (from-to)1246-1252
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume73
Issue number6
DOIs
Publication statusPublished - 2014

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Fibrin
Autoantibodies
Fibrinogen
Epitopes
Anti-Idiotypic Antibodies
Rheumatoid Arthritis
Peptides
Antibodies
Proteins
Rheumatoid Factor
Bearings (structural)
Serum
Nephelometry and Turbidimetry
Immunodominant Epitopes
Rheumatic Diseases
Arthritis
Enzyme-Linked Immunosorbent Assay
Antigens
Molecules

ASJC Scopus subject areas

  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy
  • Rheumatology

Cite this

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. / Cornillet, M.; Sebbag, M.; Verrouil, E.; Magyar, A.; Babos, F.; Ruyssen-Witrand, A.; Hudecz, F.; Cantagrel, A.; Serre, G.; Nogueira, L.

In: Annals of the Rheumatic Diseases, Vol. 73, No. 6, 2014, p. 1246-1252.

Research output: Contribution to journalArticle

Cornillet, M. ; Sebbag, M. ; Verrouil, E. ; Magyar, A. ; Babos, F. ; Ruyssen-Witrand, A. ; Hudecz, F. ; Cantagrel, A. ; Serre, G. ; Nogueira, L. / 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. In: Annals of the Rheumatic Diseases. 2014 ; Vol. 73, No. 6. pp. 1246-1252.
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title = "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",
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- 50Cit 38,42, 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 noncrossreactive 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.",
author = "M. Cornillet and M. Sebbag and E. Verrouil and A. Magyar and F. Babos and A. Ruyssen-Witrand and F. Hudecz and A. Cantagrel and G. Serre and L. Nogueira",
year = "2014",
doi = "10.1136/annrheumdis-2012-202868",
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volume = "73",
pages = "1246--1252",
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T1 - 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

AU - Cornillet, M.

AU - Sebbag, M.

AU - Verrouil, E.

AU - Magyar, A.

AU - Babos, F.

AU - Ruyssen-Witrand, A.

AU - Hudecz, F.

AU - Cantagrel, A.

AU - Serre, G.

AU - Nogueira, L.

PY - 2014

Y1 - 2014

N2 - 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- 50Cit 38,42, 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 noncrossreactive 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.

AB - 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- 50Cit 38,42, 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 noncrossreactive 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.

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