title: 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*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.
authors.affiliation: Molecular Immunogenetics Group, National Institute of Immunology, New Delhi, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Singh
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
authors.forename: Hemanta K
authors.initials: HK
authors.lastname: Kar
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Sharma
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Tembhre
authors.forename: Somesh
authors.initials: S
authors.lastname: Gupta
authors.forename: Naresh C
authors.initials: NC
authors.lastname: Laddha
authors.forename: Mitesh
authors.initials: M
authors.lastname: Dwivedi
authors.forename: Rasheedunnisa
authors.initials: R
authors.lastname: Begum
authors.forename: Rajesh S
authors.initials: RS
authors.lastname: Gokhale
authors.forename: Rajni
authors.initials: R
authors.lastname: Rani
mesh_terms: D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000235:genetics; D001665:Binding Sites / Q000276:immunology; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D059948:HLA-B44 Antigen / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017434:Protein Structure, Tertiary; D014820:Vitiligo / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D055815:Young Adult
chemical_list: D000596:Amino Acids; D015234:HLA-A Antigens; C519587:HLA-A*36:01 antigen; D059948:HLA-B44 Antigen; D059811:HLA-DRB1 Chains; C456920:HLA-DRB1*07 antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II