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

被引:0
作者
M. Cornillet
E. Verrouil
A. Cantagrel
G. Serre
L. Nogueira
机构
[1] UMR 5165 CNRS – 1056 Inserm – Toulouse University,Laboratory of “Epidermis Differentiation and Rheumatoid Autoimmunity”
[2] University Hospital of Toulouse,Laboratory of Cell Biology and Cytology
[3] University Hospital of Toulouse,Rheumatology Centre
[4] Institut Fédératif de Biologie (IFB),Laboratoire de Biologie Cellulaire et Cytologie
来源
Immunologic Research | 2015年 / 61卷
关键词
Anti-citrullinated protein autoantibodies (ACPA); B cell epitopes; Citrullinated fibrin; Rheumatoid arthritis; EBV; EBNA-1;
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学科分类号
摘要
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.
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页码:117 / 125
页数:8
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