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* Laboratory of Immunology and
Ophthalmic Genetics and Visual Function Branch, National Eye Institute, and
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
Uveitis is a complex multifactorial autoimmune disease of the eye characterized by inflammation of the uvea and retina, degeneration of the retina, and blindness in genetically predisposed patients. Using the rat model of experimental autoimmune uveitis (EAU), we previously identified three quantitative trait loci (QTL) associated with EAU on rat chromosomes 4, 12, and 10 (Eau1, Eau2, and Eau3). The primary goal of the current study is to delineate additional non-MHC chromosomal regions that control susceptibility to EAU, and to identify any QTLs that overlap with the QTLs of other autoimmune diseases. Using a set of informative microsatellite markers and F2 generations of resistant and susceptible MHC class II-matched rat strains (F344 and LEW), we have identified several new significant or suggestive QTLs on rat chromosomes 2, 3, 7, 10, and 19 that control susceptibility to EAU. A protective allele was identified in the susceptible LEW strain in the Eau5 locus at D7Wox18, and epistatic interactions between QTLs were found to influence the severity of disease. The newly identified regions (Eau4 through Eau9) colocalize with the genetic determinants of other autoimmune disease models, and to disease-regulating syntenic regions identified in autoimmune patients on human chromosomes 4q21-31, 5q31-33, 16q22-24, 17p11-q12, 20q11-13, and 22q12-13. Our results suggest that uveitis shares some of the pathogenic mechanisms associated with other autoimmune diseases, and lends support to the "common gene, common pathway" hypothesis for autoimmune disorders.
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1 This work was supported by The Intramural Research Program of the National Eye Institute, National Institutes of Health.
2 M.J.M. and A.S. contributed equally to the study.
3 Address correspondence and reprint requests to Dr. Rachel R. Caspi and Dr. Mary J. Mattapallil, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Building 10, Room 10N222, 10 Center Drive, Bethesda, MD 20892-1857. E-mail addresses: rcaspi{at}helix.nih.gov and mattapallilm{at}nei.nih.gov
4 Abbreviations used in this paper: EAU, experimental autoimmune uveitis; IRBP, interphotoreceptor retinol-binding protein; QTL, quantitative trait locus; EAE, experimental autoimmune encephalomyelitis; CIA, collagen-induced arthritis; IDDM, insulin-dependent diabetes mellitus; PIA, pristane-induced arthritis; AIA, adjuvant-induced arthritis; OR, odds ratio.
5 The online version of this article contains supplemental material.
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