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

Abstract

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% of the animals developed the disease. Low responder animals did not produce anti-IRBP IgG2a antibodies or interferon-γ. 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. Correspondence

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“…On the other hand, susceptible AIR MAX mice to pristane-induced arthritis (PIA) showed a Th2-like response to hsp65 in the initial phase of the disease differently from AIR MIN mice which were resistant and higher producers of IFN-γ [7]. Similar results were obtained in an induced model for autoimmune uveitis with an inter-photoreceptor retinoid-binding protein (IRBP) [8]. In these studies AIR MIN mice were resistant to EAU and increased serum levels of anti-IRBP IgG2a isotype were observed when compared to AIR MAX animals.…”

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“…Moreover, based on the distinct the major histocompatibility H-2 alleles of the four mouse lines and the similarities of the EAU scores, especially between the AIR MAX and L III strains, no specific MHC allele seems to be crucial for the development of the disease, as it is in inbred strains. Therefore, the genetic control of the immune characteristics during the autoimmune process in EAU is polygenic, since the interline variances were always higher than the intraline ones, and there were continuous distributions among individuals (19) .…”