Blood:不同人种共有的ADAMTS13肽可结合不同的HLA-DR

2020-04-07 MedSci原创 MedSci原创

HLA二代测序发现不同人种iTTP患者的诱因和保护因素完全不同。

免疫介导性血栓性血小板减少性紫癜(iTTP)是一种罕见的自身免疫性疾病,由中和性抗ADAMTS13自身抗体引起。在白种人中,人白细胞抗原(HLA)的等位基因DRB1*11是iTTP的诱发因素,而DRB1*04是保护性因素。但HLA在亚洲人中的作用尚不清楚。

在本研究中,研究人员通过二代测序(NGS)分析了52位日本iTTP患者的10个HLA基因位点,并将iTTP患者组的等位基因频率与对照组进行了比较。

研究结果提示,以下几个HLA等位基因是日本人群iTTP的诱发因素:DRB1*08:03(优势比[OR]: 3.06)、DRB3/4/5*blank(OR:2.3)、DQA1*01:03(OR:2.25)和DQB1*06:01(OR:2.41)。在iTTP患者中,由这4个等位基因组成的预计单倍型概率明显高于对照人群(30.8% vs 6.0%)。DRB1*15:01和DRB5*01:01是iTTP的弱保护因子;DRB1*11和DRB1*04与日本iTTP患者无明显关系。

本研究表明,在日本人和白种人之间,iTTP的诱因和保护因素有所不同。由DRB1*08:03和DRB1*11:01编码的HLA-DR分子具有不同的肽结合模体,但有趣的是,在芯片模拟模型中,它们都能够结合相同的ADAMTS13肽。

原始出处:

Kazuya Sakai, et al. HLA loci predisposing to immune TTP in Japanese: potential role of the shared ADAMTS13 peptide bound to different HLA-DR. Blood. April 6, 2020.

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    2020-04-09 般若傻瓜
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    2020-04-09 marongnuan

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