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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >The role of AIRE polymorphisms in melanoma.
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The role of AIRE polymorphisms in melanoma.

机译：AIRE多态性在黑色素瘤中的作用。

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摘要

Polymorphisms of AIRE, a transcription factor that up-regulates intrathymic expression of tissue-specific antigens including melanoma-associated antigens (MAAs), may variably affect the selection of MAAs-specific thymocytes, generating T-cell repertoires protecting or predisposing individuals to melanoma. We found that AIRE single nucleotide polymorphisms (SNPs) rs1055311, rs1800520 and rs1800522 were significantly more frequent in healthy subjects than in melanoma patients, independently from sex, age and stages of melanoma. The presence of these SNPs was associated with increased frequency of two T-cell clonotypes specific for MAGE-1 linking their protective effect to selection/expansion of MAA-specific T cells. Interestingly, mRNA transcribed on the rs1800520 SNP showed increased free energy than the wild type suggesting that its reduced stability may be responsible for the different activity of the polymorphic AIRE molecule. This finding may contribute at identifying subjects with increased risk of developing melanoma or patients with melanoma that may take benefit from immunotherapy.
机译：AIRE的多态性是一种转录因子，可上调组织特异性抗原（包括黑素瘤相关抗原（MAA））的胸腺内表达，可能会不同程度地影响MAAs特异性胸腺细胞的选择，从而产生保护或使个体易患黑素瘤的T细胞库。我们发现健康受试者的AIRE单核苷酸多态性（SNP）rs1055311，rs1800520和rs1800522比黑素瘤患者显着更频繁，而与黑素瘤的性别，年龄和阶段无关。这些SNP的存在与MAGE-1特异的两种T细胞克隆型的出现频率增加相关，并将其保护作用与MAA特异性T细胞的选择/扩增联系起来。有趣的是，在rs1800520 SNP上转录的mRNA显示的自由能比野生型增加，表明其降低的稳定性可能是造成多态性AIRE分子不同活性的原因。这一发现可能有助于确定罹患黑色素瘤风险增加的受试者或可能受益于免疫疗法的黑色素瘤患者。

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