Major histocompatibility complex and strong human leukocyte antigen–DRB1 and gender association with Vogt–Koyanagi–Harada syndrome in Mexican Mestizos

Abstract

Vogt-Koyanagi-Harada syndrome (VKH) is a multisystem autoimmune disorder mediated by cytotoxic T cells targeting melanocytes antigen(s). A strong major histocompatibility complex (MHC) association with HLA-DRB1*04:05 has been demonstrated in different populations. We investigated the contribution of HLA-A*, -B*, -C*, -DRB1*, and -DQB1* genes, belonging to the human leukocyte antigen (HLA), to the expression of VKH and we analyzed the influence of gender on the HLA association. A total of 76 patients and 256 healthy Mexican Mestizo individuals were included. HLA-A, B, C, and DQB1 typing was performed using the polymerase chain reaction, and hybridization was done using sequence specific probes. DRB1 alleles were defined by means of sequence base typing. The frequency of DRB1*04:05 (odds ratio=2.95) and DRB1*04:04 (odds ratio=2.79) were found to be significantly increased in the patients, conferring a similar risk. Gender stratification analysis showed that these alleles were associated with female gender only. No HLA class I or class II alleles were significantly deviated in males. The frequency of DRB1*04:07 was increased in the whole group, upon withdrawal from analysis the DRB1*04:04 and *04:05 positive patients. A trend of DRB1 alleles contributing to the expression of VKH is suggested: DRB1*04:05=*04:04>*04:07>*01:01>*01:02. Although none of the results were significant after the p value was corrected, the data are consistent with those in numerous other studies, suggesting that several different DRB1* alleles may be involved in the etiopathogenesis of the disease by presenting an overlapping set of ocular peptides to the T cells, which in turn may trigger the autoimmune response that is present in the patients.