HLA alleles and amino-acid signatures of the peptide-binding pockets of HLA molecules in vitiligo.

ABSTRACT

Vitiligo is a depigmenting disorder of the skin that is characterized by the loss of functional melanocytes from the lesional sites. Although the exact etiology is not understood, autoimmunity is thought to be a crucial deterministic factor. A recurring theme of several autoimmune disorders is the aberrant presentation of self-antigens to the immune system, which triggers downstream perturbations. Here we examine the role of alleles of HLA class I and class II loci to delineate vitiligo manifestation in two distinct populations. Our studies have identified three specific alleles, HLA-A*3301, HLA-B*4403, and HLA-DRB1*0701, to be significantly increased in vitiligo patients as compared with controls in both the initial study on North Indians (N=1,404) and the replication study in Gujarat (N=355) cases, establishing their positive association with vitiligo. Both generalized and localized vitiligo have the same predisposing major histocompatibility complex alleles, i.e., B*4403 and DRB1*0701, in both the populations studied, beside the differences in the frequencies of other alleles, suggesting that localized vitiligo too may be an autoimmune disorder. Significant differences in the amino-acid signatures of the peptide-binding pockets of HLA-A and HLA-B α-chain and HLA-DR ß-chain were observed between vitiligo patients and unaffected controls.