HLA Alleles and Amino-Acid Signatures of the Peptide-Binding Pockets of HLA Molecules in Vitiligo

J Invest Dermatol. 2012 Jan;132(1):124-34. doi: 10.1038/jid.2011.240. Epub 2011 Aug 11.

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*33:01, HLA-B*44:03, and HLA-DRB1*07:01, 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*44:03 and DRB1*07:01, 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 β-chain were observed between vitiligo patients and unaffected controls.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acids / genetics
  • Binding Sites / immunology
  • Child
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics
  • HLA-A Antigens / chemistry
  • HLA-A Antigens / genetics*
  • HLA-A Antigens / immunology
  • HLA-B44 Antigen / chemistry
  • HLA-B44 Antigen / genetics*
  • HLA-B44 Antigen / immunology
  • HLA-DRB1 Chains / chemistry
  • HLA-DRB1 Chains / genetics*
  • HLA-DRB1 Chains / immunology
  • Haplotypes
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / chemistry
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • India / epidemiology
  • Male
  • Middle Aged
  • Protein Structure, Tertiary
  • Vitiligo / ethnology
  • Vitiligo / genetics*
  • Vitiligo / immunology*
  • Young Adult

Substances

  • Amino Acids
  • HLA-A Antigens
  • HLA-A*36:01 antigen
  • HLA-B44 Antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*07 antigen
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II