Identification of the Risk HLA-A Alleles and Autoantigen in Han Chinese Vitiligo Patients and the Association of CD8+T Cell Reactivity with Disease Characteristics
Xiuli Yi, Tingting Cui, Shuli Li, Yuqi Yang, Jiaxi Chen, Sen Guo, Zhe Jian, Chunying Li, Tianwen Gao, Ling Liu, Kai Li
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China (mainland)
Med Sci Monit 2018; 24:6489-6497
Multiple studies have implicated a role for CD8+T cell-mediated immune response to autoantigens in vitiligo. However, the antigen-specific T lymphocyte reactivity against the peptide epitopes is diverse among different world populations. 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.
MATERIAL AND METHODS: The risk HLA-A allele was analyzed by case-control study. Enzyme linked immunospot (ELISPOT) assay was used to compare T cell reactivity to the 5 autoantigenic peptides between vitiligo patients and healthy controls, then we analyzed the association of CD8+ T cell reactivity to 2 positive peptides with disease activity and area of skin lesions.
RESULTS: The results indicated that the most frequent allele in the Han Chinese vitiligo patients was the HLA-A*02: 01 allele with a significantly higher frequency compared to controls (20.20% versus 13.79%, P=6.64×10–5). The most frequently encountered epitopes were 2 gp100 modified peptides, IMDQVPFSV and YLEPGPVTV, whereas a weak T cell reactivity against tyrosinase and Melan-A/MART-1 were evaluated. Moreover, we demonstrated that T cell reactivity against the 2 positive peptides was significantly associated with disease characteristics including disease activity and area of skin lesions.
CONCLUSIONS: Our findings showed that the HLA-A*02: 01 allele was the major risk HLA-A allele, and 2 gp100 modified peptides were identified as autoantigens and were found to be closely related to disease characteristics which might play a critical role in Han Chinese vitiligo patients.
Keywords: Autoantigens, CD8-Positive T-Lymphocytes, gp100 Melanoma Antigen, HLA-A Antigens, Vitiligo