Common genetic determinants of uveitis shared with other autoimmune disorders.
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 F(2) 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.
Mattapallil
Mary J
MJ
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA. mattapallilm@nei.nih.gov
Sahin
Azize
A
Silver
Phyllis B
PB
Sun
Shu-Hui
SH
Chan
Chi-Chao
CC
Remmers
Elaine F
EF
Hejtmancik
J Fielding
JF
Caspi
Rachel R
RR
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D018895:Microsatellite Repeats; D040641:Quantitative Trait Loci; D051381:Rats; D014605:Uveitis / Q000235:genetics* / Q000473:pathology