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.
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.
复制标题
中国汉族白癜风患者的危险 HLA-A 等位基因和自身抗原的鉴定以及 CD8 T 细胞反应性与疾病特征的关联。
DOI：
10.12659/msm.910515
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发表时间：
2018-09-16
期刊：
影响因子：
--
通讯作者：
Li K
中科院分区：
文献类型：
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作者：
Yi X;Cui T;Li S;Yang Y;Chen J;Guo S;Jian Z;Li C;Gao T;Liu L;Li K
背景：多项研究表明，CD 8 +T细胞介导的自身抗原免疫应答在白癜风中发挥作用。然而，针对肽表位的抗原特异性T淋巴细胞反应性在不同的世界人群中是不同的。本研究的目的是鉴定白癜风患者的危险HLA-A等位基因，研究中国汉族人群中CD 8 + T细胞对5种自身抗原肽的反应性，并分析CD 8 + T细胞反应性与疾病特征的关系。材料/方法采用病例对照研究的方法，对HLA-A等位基因进行分析。采用酶联免疫斑点法（ELISPOT）检测白癜风患者和健康对照者外周血T细胞对5种自身抗原肽的反应性，分析CD 8 + T细胞对2种自身抗原肽的反应性与白癜风活动性和皮损面积的关系。结果中国汉族白癜风患者中HLA-A*02：01等位基因频率最高（20.20%vs13.79%，P=6.64×10−5）。最常见的表位是2个gp 100修饰的肽，IMDQVPFSV和YLEPGPVTV，而对酪氨酸酶和Melan-A/MART-1的弱T细胞反应性进行了评估。此外，我们证明了T细胞对2种阳性肽的反应性与疾病特征（包括疾病活动性和皮肤病变面积）显著相关。结论HLA-A*02：01等位基因是汉族白癜风患者的主要危险等位基因，其中2个gp 100修饰肽为自身抗原，与患者的临床特征密切相关，可能在汉族白癜风患者中起重要作用。
Background 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/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.