#58-OR
MALE SEX INCREASES RISK FOR ACUTE ANTERIOR UVEITIS WITH THE CONTRIBUTION OF ADDITIONAL MHC-I/II LOCI IN MATCHED B*27 PATIENTS.
C. Alaez, H. Flores, L. Arellanes, A. Munguia, P. Navarro, A. Rodriguez, F. Manzanares and C. Gorodezky. Mexico City Mexico, InDRE, Dept. Immunology
Immunogenetics.
AAU is mediated by an uveal immune response in B27+ patients. It is a multifactorial intraocular disease and B27 is responsible for about 25% of the etiology, thus other genes and external factors must not be ruled out. We showed that 62.7% of Mexican patients were B27+, mainly B*2705 (OR=73). In this study we investigated the entire MHC, through STRs mapping to look for genes, other than B27. Nine MHC STRs were typed in 64 UAA patients and 72 B*27 matched healthy controls. Typing of DRB1, DQA1, DQB1 (by PCR-SSOP) and STRs were done according to the 13thIHW. For STRs, PCR fragments were analyzed in a 310 ABI Prism sequencer. The analysis of B*27 matched patients and controls demonstrated several associated susceptibility genes: D6s291-172 (OR=2.4, pc=0.01), centromeric to DPB1; DQA1*0401 (OR=5.0, pc=0.01); DQB1 *0402 (OR=3.5, pc=0.02); and DRB1*0802 (OR=4.2, pc=0.01). Gender stratification showed that these alleles are male sex associated; significance was lost in females and ORs were increased in males Vs. the whole group. Two additional STRs were sex-associated: D6s2222-245 (OR=3.5, pc=0.04) and D6s2223-174 (OR=4.3, pc= 0.03); telomeric to HLA-F. AAU is clearly a B27 polygenic disease with additional susceptibility MHC genes participating in its expression: DPB1, DRB1*0802-DQA1*0401-DQB1*0402 haplotype and D6s2223-D6s2222 region(s) contribute to susceptibility in B*27 males. Although there is no clear explanation for the interaction between sex and the MHC, hormones may influence AAU expression and severity, since down-modulation of E-selectin and IL-6 by estrogen, showed to contribute to the reduction in eye cellular infiltration in induced-AAU rats.