Epstein-Barr virus-induced autoimmune responses. II. Immunoglobulin G autoantibodies to mimicking and nonmimicking epitopes. Presence in autoimmune disease.

Abstract

During infectious mononucleosis, IgM autoantibodies are generated to a protein, p542, which contains a glycine-rich 28-mer epitope cross-reactive with the Epstein-Barr nuclear antigen-1 through Epstein-Barr nuclear antigen-l's glycine/ alanine repeat. In normal individuals it is uncommon to find IgG anti-p542, but among patients with progressive systemic sclerosis, systemic lupus erythematosus, and ulcerative colitis high IgG anti-p542 (> 3 SD above the mean of normal 20-50 yr controls) occurred frequently. Lesser elevations occurred in Sjogren's syndrome, rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease, but none with chronic hepatitis B infection. The reactive epitopes on p542 were mapped with deletion mutants, which indicated that the glycine-rich 28-mer was the major antigenic determinant, with lesser antibody responses to other epitopes. We conclude that normally there is an inability to generate IgG autoantibodies to the cross-reactive (mimicking) epitope of the p542 host protein, but that this inability is overcome in a proportion of patients with autoimmune disease. We conclude also that non-cross-reactive autoepitopes exist on p542 protein, to which IgG autoantibodies can commonly be formed in autoimmune disorders. The mechanisms responsible for the latter must involve different mechanisms than those responsible for autoantibodies to the mimicking epitope. (J. Clin. Invest. 1995Invest. . 95:1316Invest. -1327

Distribution and Phenotype of Epstein-Barr Virus-Infected Cells in Inflammatory Bowel Disease

“…30 UC patients display an enhanced humoral immune responsiveness to a recombinant protein, p542, cross-reacting with the EBNA1 protein. 31 This observation may reflect an impaired suppression of EBV-infected B cells leading to constant EBNA1 challenge, and related to the development of the autoimmune phenomena observed in UC patients.…”

EBV Latent Membrane Protein 2A Induces Autoreactive B Cell Activation and TLR Hypersensitivity

“…EBV induces infectious mononucleosis causing B cell activation and autoantibody production (11). Some Abs elicited by EBV cross-react with nuclear Ags, suggesting that antigenic mimicry is involved in the appearance of certain autoantibodies (12)(13)(14). This possibility is strengthened by the observation that EBVencoded protein, EBNA-1, contains linear epitopes similar to those of common self-antigenic targets in SLE, the B/BЈ and D peptides of ribonucleoprotein Smith (Sm) (15) and the Ro protein (16).…”

EBV-Encoded Latent Membrane Protein 1 Cooperates with BAFF/BLyS and APRIL to Induce T Cell-Independent Ig Heavy Chain Class Switching

“…However, a few latently infected B cells persist for the lifetime (36). In some predisposed subjects, latent EBV infection would favor production of IgG and IgA autoantibodies (37,38). Abnormal switching to IgG, IgA, and IgE can be also observed in adolescents with infectious mononucleosis, a self-limiting lymphoproliferative disorder secondary to acute EBV infection (34), as well as in immunocompromised subjects with EBV-associated B cell lymphoproliferative disorders (39 -41).…”