Auxiliary production of antibodies to ocular antigens in experimental autoimmune uveoretinitis

In experimental autoimmune uveoretinitis (EAU), there are concurrent autoreactive humoral and cellular immune responses. Many studies have recently focused on T-cell reactivities in EAU, while analysis of autoantibody responses to uveitogenic epitopes has been less well characterized. In this study, a defined 16-mer uveitogenic interphotoreceptor retinoid binding protein (IRBP) peptide, designated #896, was used to induce EAU. Histological analysis of eyes at day 10 demonstrated extensive leukocyte infiltration of the anterior segment, with mononuclear and plasma cells in the posterior segment. The presence of plasma cells suggests local production of antibodies within the eye. ELISA analyses of serum, aqueous, and vitreous from rats with IRBP-induced, severe EAU revealed the presence of antibodies against peptide #896. There was little difference between the serum and intraocular antibody titers, presumably due to breakdown of the blood-ocular barriers. In addition to the anti-#896-IRBP antibodies, there were detectable antibodies reactive against separate and distinct IRBP epitopes, as well as, against epitopes on retinal-S antigen. These results indicate that in #896-peptide-induced severe EAU, humoral immune responses are induced to the primary immunogen and that there is also auxiliary production of autoreactive antibodies against other epitopes present on intraocular antigens. These auxiliary responses may contribute to the immunopathogenesis of severe EAU.