Association of human leukocyte antigen and T cell message with human papillomavirus 16–positive cervical neoplasia in Japanese women
Association of human leukocyte antigen and T cell message with human papillomavirus 16–positive cervical neoplasia in Japanese women
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DOI：
10.1111/j.1525-1438.2007.00938.x
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发表时间：
2007-01
期刊：
影响因子：
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通讯作者：
Maki Saito;Mitsuo Okubo;R. Hirata;Satoru Takeda;Hiroo Maeda
中科院分区：
文献类型：
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作者：
Maki Saito;Mitsuo Okubo;R. Hirata;Satoru Takeda;Hiroo Maeda
为了研究人类白细胞抗原（HLA）单倍型与日本人群宫颈癌之间是否存在关联，我们分析了宫颈癌患者的人乳头瘤病毒（HPV）基因型、HLA I类特异性和II类等位基因以及T细胞反应。对81名患者进行了检查，其中包括62例宫颈上皮内瘤样病变（CIN）病变和19例浸润性宫颈癌（ICC）。CIN I/II组和CIN III/ICC组HPV感染率分别为68.0%（17/25）和80.4%（45/56）。对所有患者和138名当地日本对照者进行了HLA-A、HLA-B、HLA-DRB 1和HLA-DQB 1分析。HPV 16阳性的CIN III/ICC患者HLA-DRB 1 *0901等位基因频率显著高于对照组（59.3%vs29.7%，P= 0.0031，OR = 3.44）。与HLA-DQB 1等位基因相似，在HPV 16阳性CIN III/ICC患者中观察到DQB 1 *03032频率显著增加（59.3%对28.3%，P= 0.0018，OR = 3.69）。在病变中T细胞反应的分析中，Fas配体在HLA-DRB 1 *0901-DQB 1 *03032单倍型的HPV 16阳性CIN III/ICC患者中的检测频率降低。辅助性T细胞特异性信使RNA在宫颈病变中的存在支持MHC II类、辅助性T细胞、对HPV的免疫应答和宫颈癌的发展之间的关联。因此，一个特定的MHC II类单倍型，DRB 1 *0901-DQB 1 *03032，可能是日本人群宫颈癌的危险因素。
To investigate whether an association exists between human leukocyte antigen (HLA) haplotype and cervical neoplasia within the Japanese population, we analyzed the human papillomavirus (HPV) genotypes, the HLA class I specificities and class II alleles, and the T-cell responses in the lesions of patients with cervical neoplasia. Eighty-one patients, consisting of 62 cervical intraepithelial neoplasia (CIN) lesions and 19 invasive cervical cancers (ICC), were examined. The frequencies of HPV infection in the CIN I/II and CIN III/ICC groups were 68.0% (17/25) and 80.4% (45/56), respectively. All patients and 138 local Japanese controls were analyzed for HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1. For major histocompatibility complex (MHC) class II HLA-DRB1 alleles, the frequency of DRB1*0901 was significantly elevated in HPV 16–positive CIN III/ICC patients compared with controls (59.3% versus 29.7%, P= 0.0031, OR = 3.44). Similarly for the HLA-DQB1 alleles, a significant increase in the DQB1*03032 frequency was observed in HPV 16–positive CIN III/ICC patients compared with controls (59.3% versus 28.3%, P= 0.0018, OR = 3.69). In the analysis of the T-cell responses in the lesions, Fas ligand was detected at a decreased frequency in HPV 16–positive CIN III/ICC patients with the HLA-DRB1*0901–DQB1*03032 haplotype. The presence of helper T cell–specific messenger RNAs in the cervical lesions supports an association among MHC class II, helper T cells, the immune response to HPV, and the development of cervical carcinoma. Accordingly, a specific MHC class II haplotype, DRB1*0901–DQB1*03032, may be a risk factor for cervical carcinoma in the Japanese population.