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: OBJECTIVE
  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: , Epidermis Differentiation and Rheumatoid Autoimmunity' Laboratory, UMR CNRS 5165, INSERM U 1056, Toulouse III University, , Toulouse, France.
authors: M
authors: M
authors: Cornillet
authors: M
authors: M
authors: Sebbag
authors: E
authors: E
authors: Verrouil
authors: A
authors: A
authors: Magyar
authors: F
authors: F
authors: Babos
authors: A
authors: A
authors: Ruyssen-Witrand
authors: F
authors: F
authors: Hudecz
authors: A
authors: A
authors: Cantagrel
authors: G
authors: G
authors: Serre
authors: L
authors: L
authors: Nogueira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D002956:Citrulline / Q000378:metabolism*; D000939:Epitopes; D005260:Female; D005337:Fibrin / Q000276:immunology; D005338:Fibrin Fibrinogen Degradation Products / Q000276:immunology*; D005340:Fibrinogen / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology*; D012216:Rheumatic Diseases / Q000276:immunology; D012217:Rheumatoid Factor / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002956:Citrulline; D005337:Fibrin; D005340:Fibrinogen; D012217:Rheumatoid Factor
keywords: Ant-CCP; Autoantibodies; Autoimmunity; B cells; Rheumatoid Arthritis