(4) Conclusions: It remains unclear whether the <i>HLA-G</i> variants associated with vitiligo were detected because of the high linkage disequilibrium (LD) with HLA-A*02, or if the <i>HLA-A</i> variants previously reported as associated with vitiligo were detected because of the high LD with HLA-G*01:01:01:01/UTR-1, or if both genes jointly contribute to vitiligo susceptibility.
This study aimed to identify the risk HLA-A allele in vitiligo and study CD8+ T cell reactivity to 5 autoantigenic peptides in Han Chinese populations, and to analyze the association of CD8+ T cell reactivity with disease characteristics.
Vitiligo risk associated with the MHC class I region thus derives from combined quantitative and qualitative phenomena: a SNP haplotype in a transcriptional regulator that induces gain-of-function, elevating expression of HLA-A RNA in vivo, in strong linkage disequilibrium with an HLA-A allele that confers *02:01 specificity.
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.
Using tetrameric complexes of human histocompatibility leukocyte antigen (HLA) class I to identify antigen-specific T cells ex vivo, we observed high frequencies of circulating MelanA-specific, A*0201-restricted cytotoxic T lymphocytes (A2-MelanA tetramer+ CTLs) in seven of nine HLA-A*0201-positive individuals with vitiligo.