Experimental autoimmune uveitis in HLA-B27 transgenic mice.
The major histocompatibility complex (MHC) gene, HLA-B27 is strongly associated with auto-immune uveitis and spondyloarthropathies in humans. Experimental mouse models of autoimmune uveitis involve systemic immunization with the retinal autoantigen interphotoreceptor retinoid binding protein (IRBP). To assess possible roles of HLA-B27 in autoimmune uveitis, as well as to investigate a possible new animal model of human uveitis, inbred strains of C57BL/6 and C57BL/6 possessing the human HLA-B27 or HLA-A2 transgene were immunized with IRBP emulsified in complete 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 uveitis. Fifty percent of eyes from the background C57BL/6 strain developed 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 postinjection with an average clinical score of 2.0. Pathologically, a mild vitritis was present. Uveitis developed in only 20% of B27 transgenic mice and reached a peak on day 28. The average EAU score in diseased animals was 4.5. A dense retinitis and panuveitis was associated with severe vitritis. We conclude that the presence of the B27 gene is associated with a decreased incidence and slower rate of onset of EAU following immunization with IRBP; however, EAU may be more severe in the HLA-B27 expressing animals who do develop disease.
Willbanks
G A
GA
University of Toronto, Ontario, Canada.
Rootman
D S
DS
Jay
V
V
Wiggert
B
B
Chamberlain
J
J
Inman
R D
RD
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D005136:Eye Proteins / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012177:Retinol-Binding Proteins / Q000008:administration & dosage / Q000276:immunology; D019076:Transgenes / Q000276:immunology*; D014605:Uveitis / Q000209:etiology / Q000235:genetics*; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D015789:HLA-A2 Antigen; D015796:HLA-B27 Antigen; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial