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A6.6 In RA patients, antibodies to the citrullinated peptide EBNA35-58Cit from epstein-barr nuclear antigen-1 crossreact with the citrullinated fibrin peptide β60-74Cit60,72,74
  1. M Cornillet1,2,
  2. E Verrouil2,3,
  3. A Cantagrel3,
  4. G Serre1,2,
  5. L Nogueira1,2
  1. 1Laboratory of “Epidermis Differentiation and Rheumatoid Autoimmunity”, UMR 5165 CNRS–1056 Inserm–Toulouse University, Toulouse, France
  2. 2Laboratory of Cell Biology and Cytology, University Hospital of Toulouse, Toulouse, France
  3. 3Rheumatology Center, University Hospital of Toulouse, Toulouse, France

Abstract

Background Among the Rheumatoid Arthritis (RA)-specific antibodies to citrullinated proteins/peptides (ACPA), the autoantibodies to citrullinated fibrinogen (AhFibA) target 2 immunodominant epitopes borne by the peptides α36-50Cit38,42 and β60-74Cit 60,72,74. RA sera also contain antibodies to the citrullinated peptide EBNA35-58Cit derived from EBNA-1, a protein of Epstein Barr Virus (EBV).

Objectives To analyse the diagnostic value of anti-EBNA35-58Cit antibodies and their relationships with AhFibA, anti-α36-50Cit38,42 and anti-β60-74Cit60,72,74 autoantibodies.

Methods A large representative series of 181 established RA and 436 non-RA rheumatic diseases was tested by ELISA for AhFibA, anti-CCP2, anti-α36-50Cit38,42, anti-β60-74Cit60,72,74 and anti-EBNA35-58Cit antibodies. Diagnostic indexes, correlations and concordances between tests were analysed. In addition, cross-reactivity of anti-EBNA35-58Cit toward β60-74Cit60,72,74 and α36-50Cit38,42 was evaluated in competition assays.

Results At a diagnostic specificity of 98.5%, the diagnostic sensitivity of anti-EBNA35-58Cit antibodies was 36%, similar to that of anti-α36-50Cit38,42 (41%) but significantly lower than that of anti-β60-74Cit60,72,74 (62%) autoantibodies. Moreover, almost all sera containing anti-EBNA35-58 antibodies were reactive to citrullinated fibrinogen, 91% to β60-74Cit60,72,74, and 43% to α36-50Cit38,42. Anti-EBNA35-58 antibodies titres significantly correlated with those of anti-β60-74Cit60,72,74 (r = 0.482), AhFibA (r = 0.504) and anti-CCP2 (r = 0.479) but not with those of anti-α36-50Cit38,42 (r = 0.051). Competition assays revealed that anti-EBNA35-58Cit antibodies are highly crossreactive with anti-β60-74Cit60,72,74 but not with anti-α36-50Cit38,42 autoantibodies.

Conclusions Anti-EBNA35-58Cit antibodies are present in 36% of AhFibA-positive patients with established RA. They are highly crossreactive with the autoantibodies to the immunodominant fibrin peptide β60-74Cit60,72,74. That suggests that the two antibodies have the same fine specificity and therefore correspond to a same subpopulation of ACPA.

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