补体系统基因的罕见变异与儿科全源性造血干细胞移植后的内皮损伤有关
Lilli Leimi1, Jessica R Koski2,3,4, Outi Kilpivaara2,3,4,5
1Pediatric Research Center, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Frontiers in immunology
|September 29, 2023
概括
补体系统中的遗传变异与血液造血干细胞移植 (HSCT) 后的内皮病相关. 这些发现表明,补体系统异常可能使患者在HSCT后易患血管并发症.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 血液学 血液学 血液学
背景情况:
- 内皮功能障碍是血液造血干细胞移植 (HSCT) 后的一个重大并发症.
- 补体系统是先天免疫的关键组成部分,与各种内皮疾病有关.
- 之前的研究在儿科HSCT患者中发现了血管并发症,如毛细血管泄漏综合征 (CLS),静脉封闭性疾病/阴影阻塞综合征 (VOD/SOS) 和血栓微血管病变 (TMA).
研究的目的:
- 研究补充系统基因中的遗传变异在经历HSCT后内皮病变的患者中所起的作用.
- 识别与移植后内皮质变异风险增加相关的特定补充基因变异.
主要方法:
- 对109名患有移植前DNA的儿科HSCT患者进行了回顾性分析.
- 进行了全外体序列测序 (WES),专注于编码补充元件的41个基因.
- 基因负担测试进行,将患者变异与芬兰gnomAD人口进行比较.
主要成果:
- 近一半的患者 (45.9%) 在补充基因中携带罕见的生殖系变异.
- 终端通路基因 (C6,C9) 和乳素通路基因 (MASP1) 的变异在内皮质变异症患者中观察到.
- 与芬兰普通人口相比,HSCT患者在25个补充基因中的14个中发现了误解变异的显著丰富.
结论:
- 补体系统组件中的遗传变异与HSCT后的内皮病相关.
- 这些发现凸显了HSCT接受者对血管并发症的潜在遗传倾向.
- 对补充系统遗传学的进一步研究可能会确定与HSCT相关的内皮病变的新型治疗点.
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