EXPERIMENTAL AUTOIMMUNE UVEITIS IN HLA-B27 TRANSGENIC MICE

The major histocompatibility complex (MHC) gene, HLA-B27 is strongly a ssociated with autoimmune uveitis and spondyloarthropathies in humans. Experimental mouse models of autoimmune uveitis involve systemic immu nization with the retinal autoantigen interphotoreceptor retinoid bind ing protein (IRBP). To assess possible roles of HLA-B27 in autoimmune uveitis, as well as to investigate a possible new animal model of huma n uveitis, inbred strains of C57BL/6 and C57BL/6 possessing the human HLA-B27 or HLA-A2 transgene were immunized with IRBP emulsified in com plete Freund's adjuvant (CFA). Dilated eye examinations were performed to assess the timing and clinical course of any ensuing uveitis. Mice were sacrificed 3 to 4 weeks postinjection and the eyes submitted for histopathologic analysis. CFA alone did not produce any clinical uvei tis. Fifty percent of eyes from the background C57BL/6 strain develope d uveitis as early as 10 days postinjection. Of the eyes demonstrating uveitis, an average clinical score of 2.5 was present. Pathologically , a moderate scleritis and anterior uveitis was present. Fifty percent of A2 transgenic eyes developed uveitis as early as 14 days postinjec tion with an average clinical score of 2.0. Pathologically, a mild vit riitis was present. Uveitis developed in only 20% of B27 transgenic mi ce and reached a peak on day 28. The average EAU score in diseased ani mals was 4.5. A dense retinitis and panuveitis was associated with sev ere vitritis. We conclude that the presence of the B27 gene is associa ted with a decreased incidence and slower rate of onset of EAU followi ng immunization with IRBP; however, EAU may be more severe in the HLA- B27 expressing animals who do develop disease. (C) American Society fo r Histocompatibility and Immunogenetics, 1997.