Infection risk associated with clonal hematopoiesis of indeterminate potential is partly mediated by hematologic cancer transformation in the UK Biobank.
Infection risk associated with clonal hematopoiesis of indeterminate potential is partly mediated by hematologic cancer transformation in the UK Biobank.
复制标题
在英国生物库中，与不确定潜力的克隆造血相关的感染风险部分是由血液癌转化介导的。
DOI：
10.1038/s41375-023-02023-7
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发表时间：
2023
期刊：
影响因子：
11.4
通讯作者：
Bick,AlexanderG
中科院分区：
文献类型：
--
作者：
Vlasschaert,Caitlyn;Akwo,Elvis;Robinson-Cohen,Cassianne;Cook,ElinaK;Lanktree,MatthewB;Rauh,MichaelJ;Bick,AlexanderG
不确定潜能克隆造血 (CHIP) 是最近描述的一种病症，其中相当大比例的个体循环血细胞源自单个突变的造血干细胞 [1]。 CHIP 的发生是衰老的常见后果：超过 10% 的 65 岁以上个体受到影响。虽然 CHIP 是骨髓系血液癌的前兆状态，但恶性转化是一种罕见的事件：每年只有 0.03-1% 的 CHIP 病例转化为癌症 [2]。重要的是，CHIP 与过早死亡风险增加和跨器官系统慢性疾病负担增加有关 [3-8]。这种全慢性疾病风险的一个核心机制是受 CHIP 影响的白细胞（特别是单核细胞和巨噬细胞）促炎信号的上调 [3, 7-10]。关于 CHIP 在感染风险中的作用以及 CHIP 对感染中重要的白细胞功能（如中性粒细胞）的潜在影响，已发表的研究相对较少；迄今为止的文献大多仅限于评估 CHIP 在 COVID-19 和 HIV 感染中的作用的流行病学研究[11-13]。一种相关但不同的克隆血液状态，即克隆镶嵌染色体改变，与多种类型感染的风险增加有关[14]。在这项工作中，我们评估了 CHIP 与感染风险之间的关联。我们使用来自英国生物银行 (UKB) 的大型观察性队列研究的数据来确定 12 年期间入组时的 CHIP 状态与败血症、细菌和病毒感染事件之间的关联。 UKB 是一个大型观察队列，由 2006 年至 2010 年间登记的超过 500,000 名居住在英国的个人组成。在基线时收集人口统计数据，包括年龄、性别和健康习惯，并从电子健康记录（医院和全科医生记录）、癌症登记和死亡登记中持续收集临床结果数据。中位数为 12.4 年 [四分位距，11.6-13.1]
Clonal hematopoiesis of indeterminate potential (CHIP) is a recently described condition wherein a sizeable proportion of an individualLs circulating blood cells are derived from a single mutated hematopoietic stem cell [1]. The development of CHIP is a common consequence of aging: more than 10% of individuals over age 65 are affected. While CHIP is a precursor state for myeloid lineage hematologic cancers, malignant transformation is a rare event: only 0.03-1% of CHIP cases transform to cancer per year [2]. Importantly, CHIP has been associated with an increased risk of premature death and a greater burden of chronic disease across organ systems [3-8]. A central mechanism for this panchronic disease risk is the upregulation of pro-inflammatory signaling by CHIP-affected white blood cells, particularly monocytes and macrophages [3, 7-10]. There is a comparative paucity of published studies on the role of CHIP in infection risk and on the potential effects of CHIP on the function of white blood cells important in infection such as neutrophils; the literature to date is mostly limited to epidemiologic studies assessing the role of CHIP in COVID-19 and HIV infections [11-13]. A related but distinct clonal blood state, clonal mosaic chromosomal alterations, has been associated with an increased risk for diverse types of infection [14].In this work, we assess the association between CHIP and infection risk. We use data from a large observational cohort study, the UK Biobank (UKB), to determine the association between CHIP status at enrollment with incident sepsis, bacterial, and viral infections over a 12-year period. The UKB is a large observational cohort comprised of over 500,000 individuals residing in the United Kingdom who were enrolled between 2006 and 2010. Demographic data, including age, sex, and health habits, were collected at baseline, and clinical outcome data are collected on an ongoing basis from electronic health records (hospital and general practitioner records), cancer registries, and death registries. A median of 12.4 years [interquartile range, 11.6-13.1] of