HLA-DQB1*05亚型,而不是DRB1*10:01在抗IgLON5疾病中的风险中介
Selina M Yogeshwar1,2,3, Sergio Muñiz-Castrillo1, Lidia Sabater4
1Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Brain : a journal of neurology
|March 1, 2024
概括
抗IgLON5疾病是一种罕见的自身免疫性脑炎,与特定的HLA-DQ基因型密切相关. 这些遗传因素影响疾病发病,并可能触发T细胞对IgLON5的反应,从而导致自身免疫.
科学领域:
- 神经免疫学 神经免疫学
- 遗传学 遗传学 是一个
- 自免疫性疾病 自免疫性疾病
背景情况:
- 含有1 (IgLON5) 疾病的抗免疫球蛋白类域是一种罕见的自身免疫性脑炎,具有多种神经症状.
- 之前的研究表明与人类白细胞抗原 (HLA) 的等位基因存在关联,特别是HLA-DRB1*10:01∼DQB1*05:01.
研究的目的:
- 调查抗IgLON5疾病中人类白细胞特异抗原 (HLA) 的相关性.
- 探索已识别的HLA等位基因在疾病发病过程中的功能作用.
主要方法:
- 87名抗IgLON5患者的多中心HLA基因定型.
- 对HLA-DQ和HLA-DR关联的分析.
- 竞争结合试验用于评估IgLON5对HLA-DQ分子的结合.
- 使用IgLON5的T细胞激活试验.
主要成果:
- 在85%的患者中,与HLA-DQ相比,与HLA-DR有更强的关联,特别是与HLA-DQA1*01:05∼DQB1*05:01,HLA-DQA1*01:01∼DQB1*05:01,HLA-DQA1*01:04∼DQB1*05:03.
- 这些HLA-DQ基因型与晚期发病年龄相关,最多延迟11年.
- 功能性测试显示,改性IgLON5对与风险相关的HLA-DQ受体的优先结合,以及由脱胺IgLON5激活T细胞的激活.
结论:
- 这些发现强烈暗示HLA-DQ等位基因对抗IgLON5疾病的敏感性.
- HLA-DQ介导的T细胞对改性IgLON5的反应可能是启动自身免疫的关键机制.
- 这些结果凸显了HLA-DQ在抗IgLON5疾病的发病过程中的重要性.
关键词:
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