Pathophysiological links between rheumatoid arthritis and the Epstein-Barr virus: an update.
Numerous associations have been documented between the Epstein-Barr virus (EBV) and rheumatoid arthritis (RA). Thus, anti-EBV antibody titers are higher in RA patients than in healthy controls. Lymphocytes from RA patients show impaired responses to EBV. Several EBV antigens share similarities with self antigens; more specifically, the glycine/alanine repeats in EBNA-1 resemble synovial proteins and the EBV gp110 glycoprotein contains a copy of the shared epitope. Cell-mediated responses to EBV replicative cycle proteins and to gp110 have been documented in joint fluid from RA patients. In situ hybridization and PCR techniques have identified EBV antigens and genetic material within the rheumatoid synovium, albeit with variable yields. The EBV burden in peripheral blood mononuclear cells is higher in RA patients than in controls. EBNA-1 can undergo citrullination, and the EBV can induce antibodies to citrullinated peptides. RA patients are at increased risk for lymphoma, including EBV-associated lymphoma. Despite these multiple and complex links between EBV and RA, proof of a causal association is lacking. EBV infection may contribute indirectly to the pathophysiology of RA by impairing immune control of EBV replication, causing increased exposure to EBV antigens and, thereby, chronic inflammation. The effect of biotherapies for RA on EBV-host relations needs to be investigated.
Toussirot
Eric
E
Rheumatology Department, Jean Minjoz Teaching Hospital, Boulevard A. Fleming, 25030 Besançon, France. etoussirot@chu-besancon.fr
Roudier
Jean
J
D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D015551:Autoimmunity; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000503:physiopathology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007596:Joints / Q000276:immunology
D000956:Antigens, Viral