title: Epstein-Barr virus as an etiological agent in primary Sjögren's syndrome.
abstract: It is proposed that the initiating event in primary Sjögren's syndrome is infection with Epstein-Barr virus (EBV), and that the autoimmune exocrinopathy that progresses to keratoconjunctivitis sicca and xerostomia is a sequel to this. Our hypothesis is based on the findings that the antinuclear antibody, anti-La(SS-B), is a marker of primary Sjögren's syndrome, and that anti-La reacts with a ribonucleoprotein, the La autoantigen, to which bind not only all cellular RNAs transcribed by RNA polymerase III, but also the viral RNAs, EBER 1 and EBER 2, encoded by the Epstein-Barr virus (EBV). It is proposed that during EBV infection, there are multiple copies of the EBERs available to bind to the La ribonucleoprotein and when infection occurs in subjects who have an impaired T cell-mediated response to EBV, and who are genetically predisposed to autoimmunity, there is loss of immunological tolerance to La with production of anti-La (SS-B). Thus the inflammatory process in exocrine glands which culminates in the sicca syndrome is due to the combined effects of chronic EBV infection and autoimmunity. Two patients are briefly described in whom primary Sjögren's syndrome appeared to be a direct consequence of EBV infection. The hypothesis engages the question of the respective roles of virus infection, specific immunodeficiency to virus, immunogenetic constitutive influences and an autoimmune response to a ribonucleoprotein antigen in the genesis of a particular organ-specific inflammatory reaction.
mesh_terms: D000914:Antibodies, Viral / Q000032:analysis; D001323:Autoantibodies / Q000096:biosynthesis; D003429:Cross Reactions; D005260:Female; D006566:Herpesviridae Infections / Q000150:complications*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008297:Male; D012859:Sjogren's Syndrome / Q000209:etiology* / Q000235:genetics / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes