美国哈佛和麻省理工学院的布罗德研究所Pradeep Natarajan研究组发现，造血镶嵌染色体改变 (mCA)增加各种感染的风险。这一成果发表于2021年6月7日出版的《自然-医学》杂志上。

他们表明mCA易导致多种类型的感染。他们在五个生物库中分析了来自 768,762 名在采集 DNA 时没有血液学癌症个体的 mCA。扩大的常染色体 mCA 与多种事件感染相关（风险比 (HR) 1.25；95% 置信区间 (CI) = 1.15–1.36；P = 1.8 × 10-7），包括败血症（HR 2.68；95% CI2 5– = 3.19；P = 3.1 × 10-28），肺炎（HR 1.76；95% CI = 1.53-2.03；P = 2.3 × 10-15），消化系统感染（HR1.51； 95%CI=1.32-1.73；P = 2.2 × 10-9）和泌尿生殖系统感染（HR 1.25；95% CI = 1.11–1.41；P = 3.7 × 10-4）。一项扩展 mCA 的全基因组关联研究确定了 63 个基因座，这些基因座在免疫细胞的转录调控位点富集。这些结果表明 mCA 是免疫受损的标志，并增加了感染的易感性。

据介绍，衰老是传染病的主要危险因素，但衰老与传染病风险之间的联系机制尚不完全清楚。从血液来源的 DNA 基因分型中检测到的衰老相关的mCA，这是指示克隆造血的结构体细胞变异，并且与异常的白细胞计数、血液系统恶性肿瘤和死亡率相关。

附：英文原文

Title: Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection

Author: Seyedeh M. Zekavat, Shu-Hong Lin, Alexander G. Bick, Aoxing Liu, Kaavya Paruchuri, Chen Wang, Md Mesbah Uddin, Yixuan Ye, Zhaolong Yu, Xiaoxi Liu, Yoichiro Kamatani, Romit Bhattacharya, James P. Pirruccello, Akhil Pampana, Po-Ru Loh, Puja Kohli, Steven A. McCarroll, Krzysztof Kiryluk, Benjamin Neale, Iuliana Ionita-Laza, Eric A. Engels, Derek W. Brown, Jordan W. Smoller, Robert Green, Elizabeth W. Karlson, Matthew Lebo, Patrick T. Ellinor, Scott T. Weiss, Mark J. Daly, Chikashi Terao, Hongyu Zhao, Benjamin L. Ebert, Muredach P. Reilly, Andrea Ganna, Mitchell J. Machiela, Giulio Genovese, Pradeep Natarajan

Issue&Volume: 2021-06-07

Abstract: Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from 768,762 individuals without hematological cancer at the time of DNA acquisition across five biobanks. Expanded autosomal mCAs were associated with diverse incident infections (hazard ratio (HR) 1.25; 95% confidence interval (CI)=1.15–1.36; P=1.8×107), including sepsis (HR 2.68; 95% CI=2.25–3.19; P=3.1×1028), pneumonia (HR 1.76; 95% CI=1.53–2.03; P=2.3×1015), digestive system infections (HR 1.51; 95% CI=1.32–1.73; P=2.2×109) and genitourinary infections (HR 1.25; 95% CI=1.11–1.41; P=3.7×104). A genome-wide association study of expanded mCAs identified 63 loci, which were enriched at transcriptional regulatory sites for immune cells. These results suggest that mCAs are a marker of impaired immunity and confer increased predisposition to infections.

DOI: 10.1038/s41591-021-01371-0

Source: https://www.nature.com/articles/s41591-021-01371-0