HLA-DR is strongly associated with Vogt-Koyanagi-Harada disease in Mexican Mestizo patients

Abstract

The strong association found with HLA-DR4 and the slight DR1 increase shown in Mexican patients with VKH suggest that a common shared sequence present in the third hypervariable region of DRB1 genes is relevant for the expression of the disease. The stronger association with DR4 than the one with DQ8 suggests that the DR locus carries the primary susceptibility genes involved in the pathogenesis of VKH.

HLA-DRB1 and -DQB1 alleles in mestizo patients with Vogt-Koyanagi-Harada’s disease in Southern California

“…Indeed, HLA-DR1 had a higher relative risk than HLA-DR4 (4.11 vs 1.96, respectively) in this population [3]. In contrast, although both HLA-DR1 and -DR4 serotypes were also found in mestizo patients with VKH disease in a study from Mexico City, only HLA-DR4 was significantly increased compared with controls [4]. Using DNA-based techniques to look at HLA alleles rather than HLA serotypes in the same population, HLA-DRB1*0101 was associated with disease and HLA-DRB1*01 or HLA-DRB1*04 subtypes were found in 89% [5].…”

“…While self-identification is not an ideal method for classifying individuals on the basis of race [8], it has been used previously in studies of HLA gene frequencies, including the National Marrow Donor Program [9]. This approach allowed us to establish a range of HLA alleles associated with VKH disease in non-Asian population, and enabled us to compare our results with other populations of mestizo patients with VKH disease [4,5].…”

KIR and HLA gene combinations in Vogt-Koyanagi-Harada disease

“…Ex vivo [1] and in silico [2] studies suggest that it is a T-lymphocyte-mediated disease and that specific auto-antigens, tyrosinase, and tyrosinase-related proteins play a role in disease pathogenesis. Strong associations with the HLA-DRB1*0405 subtype have been described in Japanese and Korean populations [3,4] but not in Mestizo populations [5,6]. It is likely that other genetic components of the immune response play a role in conferring risk for disease.…”

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

“…It was later reported, in 29 patients, also from Southern California, that there was an increased frequency of DRB1*04:04 and *04:07, although significance was lost after correction [21]. Two studies done with Mexican Mestizo patients from the highlands of Mexico were published by our group [22,23]. The first one, done by serologic typing only, showed that 85.4% of the patients had either DR4 or DR1, with a stronger DR4 association; no class I antigen was then found to be associated with VKH [22].…”

“…Two studies done with Mexican Mestizo patients from the highlands of Mexico were published by our group [22,23]. The first one, done by serologic typing only, showed that 85.4% of the patients had either DR4 or DR1, with a stronger DR4 association; no class I antigen was then found to be associated with VKH [22]. In the second study, an overall increase of DRB1*04 as a whole was reported in the patients, with no contribution of any specific subtype.…”