The anti-IRBP IgG1 and IgG2a response does not correlate with susceptibility to experimental autoimmune uveitis

Susceptibility to experimental autoimmune uveitis (EAU) in inbred mice has been associated with a dominant Th1 response. Elevated anti-inter-photoreceptor retinoid-binding protein (anti-IRBP) IgG2a/IgG1 antibody ratios have been implicated as candidate markers to predict disease severity. In the present study, both the anti-IRBP antibody isotype and severity of EAU phenotypes were examined in 4 non-isogenic genetically selected mouse lines to determine if they can be used as general markers of disease. Mice between 8 and 12 weeks old selected for high (H III) or low (L III) antibody response and for maximum (AIR MAX) or minimum (AIR MIN) acute inflammatory reaction (AIR) were immunized with IRBP. Each experiment was performed with at least 5 mice per group. EAU was evaluated by histopathology 21 days after immunization and the minimal criterion was inflammatory cell infiltration of the ciliary body, choroid and retina. Serum IgG1- and IgG2a-specific antibodies were determined by ELISA. EAU was graded by histological examination of the enucleated eyes. The incidence of EAU was lower in AIR MIN mice whereas in the other strains approximately 40 percent of the animals developed the disease. Low responder animals did not produce anti-IRBP IgG2a antibodies or interferon-gamma. No correlation was observed between susceptibility to EAU and anti-IRBP isotype profiles. Susceptibility to EAU is related to the intrinsic capacity to mount higher inflammatory reactions and increased production of anti-IRBP IgG2a isotype is not necessarily a marker of this immunologic profile.

Cellular immune response to retinal S-antigen & interphotoreceptor retinoid binding protein fragments in idiopathic human uveitis.

The role of retinal antigens in idiopathic human uveitis has been studied in 38 patients of uveitis, and 30 patients of systemic connective tissue disease (CTD) and 30 healthy volunteers. Lymphocyte proliferative responses were tested in vitro against native S-antigen, its uveitopathogenic peptides (peptide M, peptide G), yeast histone H3 peptide and uveitopathogenic fragment of interphotoreceptor retinoid binding protein (IRBP: R16) to establish their role in pathogenesis of human uveitis. Seven patients with uveitis, and none among CTD patients and healthy volunteers, responded (stimulation index > 3) to at least one retinal antigen used. One uveitis patient showed response to native S-antigen, peptide M and yeast histone H3. One responded to both S-antigen and peptide M and another responded to both peptide G and R16 peptide. Two responded to S-antigen only, one to peptide M and one to peptide G. In addition, one uveitis patient responded to yeast histone H3 only. These results suggest that retinal antigens may play a role in the etiopathogenesis of a subset of idiopathic human uveitis.