潜力不确定的克隆造血和自身免疫性疾病的风险。

IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Hanzhang Wu, Jiahe Wei, Yuefeng Yu, Ningjian Wang, Xiao Tan
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引用次数: 0

摘要

背景:不确定电位克隆造血(CHIP)的特点是携带白血病前突变的血细胞的年龄相关扩增,与免疫衰老有关。本研究旨在探讨CHIP与自身免疫性疾病之间的关系。方法:我们分析了来自456692名英国生物银行参与者的基线数据,这些参与者具有可用的全外显子组序列。主要结果为19例自身免疫性疾病。使用Cox回归评估任何CHIP(变异等位基因分数≥2%)、大CHIP克隆(变异等位基因分数≥10%)和基因特异性CHIP亚型与自身免疫性疾病发病率之间的关系。通过中介分析探讨炎症在CHIP与自身免疫性疾病之间的联系中的作用。结果:在基线时,我们发现了17433个小CHIP和11970个大CHIP。患有CHIP的受试者患克罗恩病的风险分别高出44%和43%,患牛皮癣的风险分别高出25%和33%,患类风湿关节炎的风险分别高出13%和14%,患血管炎的风险分别高出35%和55%。CHIP状态的参与者与炎症标志物水平升高相关,包括白细胞、血小板、中性粒细胞和中性粒细胞与淋巴细胞比率,克罗恩病的总介导比率为16.3%,牛皮癣为7.1%,类风湿性关节炎为23.2%,血管炎为7.2%。结论:CHIP与多种自身免疫性疾病的发生风险增加相关,包括克罗恩病、牛皮癣、血管炎和类风湿性关节炎,可能由炎症水平升高介导。未来的研究需要澄清这些关联背后的机制,并探索降低相关风险的潜在干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clonal hematopoiesis of indeterminate potential and the risk of autoimmune diseases.

Background: Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related expansion of blood cells carrying preleukemic mutations, is associated with immune aging. This study aimed to investigate the association between CHIP and established autoimmune diseases.

Methods: We analyzed baseline data from 456,692 UK Biobank participants with available whole-exome sequences. The primary outcome was 19 autoimmune disorders. Associations among any CHIP (variant allele fraction ≥2%), large CHIP clones (variant allele fraction ≥10%), and gene-specific CHIP subtypes with the incidence of autoimmune diseases were assessed using Cox regression. Mediation analysis was performed to explore the role of inflammation in the link between CHIP and autoimmune diseases.

Results: We identified 17,433 any CHIP and 11,970 large CHIP at baseline. Participants with any and large CHIP were associated with 44% and 43% higher risk for Crohn's disease, 25% and 33% higher risk for psoriasis, 13% and 14% higher risk for rheumatoid arthritis, and 35% and 55% higher risk for vasculitis, respectively. Participants with CHIP status were associated with increased levels of inflammatory markers, including white blood cell, platelets, neutrophils, and neutrophil-to-lymphocyte ratio, with overall mediation ratios of 16.3% for Crohn's disease, 7.1% for psoriasis, 23.2% for rheumatoid arthritis, and 7.2% for vasculitis.

Conclusions: CHIP was associated with an increased risk for incident multiple autoimmune diseases, including Crohn's disease, psoriasis, vasculitis, and rheumatoid arthritis, potentially mediated by elevated inflammatory levels. Future research is needed to clarify the mechanisms underlying these associations and to explore potential interventions to reduce the associated risk.

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来源期刊
Journal of Internal Medicine
Journal of Internal Medicine 医学-医学:内科
CiteScore
22.00
自引率
0.90%
发文量
176
审稿时长
4-8 weeks
期刊介绍: JIM – The Journal of Internal Medicine, in continuous publication since 1863, is an international, peer-reviewed scientific journal. It publishes original work in clinical science, spanning from bench to bedside, encompassing a wide range of internal medicine and its subspecialties. JIM showcases original articles, reviews, brief reports, and research letters in the field of internal medicine.
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