title: In ACPA-positive RA patients, antibodies to EBNA35-58Cit, a citrullinated peptide from the Epstein-Barr nuclear antigen-1, strongly cross-react with the peptide β60-74Cit which bears the immunodominant epitope of citrullinated fibrin.
abstract: Although several infectious agents and particularly Epstein-Barr virus (EBV) have been suspected to be involved in aetiology of rheumatoid arthritis (RA), their role still remains elusive. Almost 80% of RA sera contain antibodies to citrullinated proteins/peptides. Among them, the autoantibodies to citrullinated human fibrinogen (AhFibA) are composed of two non-cross-reactive subsets directed to immunodominant epitopes borne by the α36-50Cit and β60-74Cit fibrin peptides. RA sera also contain antibodies towards the citrullinated EBNA35-58Cit peptide derived from the EBNA-1 protein of EBV. Here, using a large cohort of RA patients and controls, we showed that for a diagnostic specificity of 98.5%, 47% of the AhFibA-positive patients were anti-EBNA35-58Cit-positive and that almost all (98.5%) the anti-EBNA35-58Cit-positive were AhFibA-positive, whereas 86% were anti-β60-74Cit-positive and only 43% anti-α36-50Cit-positive. AhFibA, anti-EBNA35-58Cit- and anti-β60-74Cit-antibody titres were significantly correlated. Competition assays showed that anti-EBNA35-58Cit antibodies are highly cross-reactive with the β60-74Cit peptide. The demonstration that a citrullinated peptide derived from the EBNA-1 protein of EBV presents a molecular mimicry with human citrullinated fibrin constitutes an additional argument for a possible role of EBV in RA aetiopathogeny.
authors.affiliation: Laboratory of "Epidermis Differentiation and Rheumatoid Autoimmunity", UMR 5165 CNRS - 1056 Inserm - Toulouse University, Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Cornillet
authors.forename: E
authors.initials: E
authors.lastname: Verrouil
authors.forename: A
authors.initials: A
authors.lastname: Cantagrel
authors.forename: G
authors.initials: G
authors.lastname: Serre
authors.forename: L
authors.initials: L
authors.lastname: Nogueira
mesh_terms: D000906:Antibodies / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016022:Case-Control Studies; D003429:Cross Reactions / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry / Q000276:immunology*; D005337:Fibrin / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D010455:Peptides / Q000276:immunology*
chemical_list: D000906:Antibodies; D019309:Epstein-Barr Virus Nuclear Antigens; D016056:Immunodominant Epitopes; D010455:Peptides; D005337:Fibrin; C417029:EBV-encoded nuclear antigen 1