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-α36-50Cit₃₈,₄₂, 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.

• Authors: M Cornillet, M Sebbag, E Verrouil, A Magyar, F Babos, A Ruyssen-Witrand, F Hudecz, A Cantagrel, G Serre, L Nogueira
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 73 Issue 6 Pg. 1246-52 (Jun 2014) ISSN: 1468-2060 [Electronic] England
• PMID: 23636655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Epitopes
• Fibrin Fibrinogen Degradation Products
• Peptide Fragments
• Peptides, Cyclic
• cyclic citrullinated peptide
• Citrulline
• Fibrin
• Fibrinogen
• Rheumatoid Factor

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Arthritis, Rheumatoid (immunology)
• Autoantibodies (immunology)
• Case-Control Studies
• Citrulline (metabolism)
• Epitopes
• Female
• Fibrin (immunology)
• Fibrin Fibrinogen Degradation Products (immunology)
• Fibrinogen (immunology)
• Humans
• Male
• Middle Aged
• Peptide Fragments (immunology)
• Peptides, Cyclic (immunology)
• Rheumatic Diseases (immunology)
• Rheumatoid Factor (immunology)
• Young Adult