自身炎症和自身免疫疾病中的体细胞突变

IF 29.4 1区 医学 Q1 RHEUMATOLOGY Nature Reviews Rheumatology Pub Date : 2024-10-11 DOI:10.1038/s41584-024-01168-8
Sofia Torreggiani, Flore S. Castellan, Ivona Aksentijevich, David B. Beck
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引用次数: 0

摘要

体细胞突变(也称为获得性突变)是一种常见的、与年龄有关的过程,发生在全身所有细胞中。体细胞突变通常与恶性过程有关,但在过去十年中,体细胞突变与包括风湿病在内的良性疾病的因果关系越来越密切。在此,我们概述了体细胞突变对复杂和单基因免疫性疾病的贡献,并详细回顾了与这些病因相关的独特方面。体细胞突变可导致早发或晚发的风湿性单基因疾病,但也有助于复杂的炎症和免疫介导疾病的发病机制,影响疾病的进展并定义新的临床亚型。尽管变异等位基因比例较低的变异也可能致病,但随着时间的推移,克隆动态会导致变异细胞比例发生变化,从而可能对个体产生表型后果。因此,体细胞突变和克隆扩增对基因检测和咨询具有重要意义。随着临床实践中对体细胞疾病认识的提高以及技术和生物信息流程的改进,我们推测导致炎症的各种基因的体细胞突变将不断扩大,尤其是在晚期发病的疾病中。
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Somatic mutations in autoinflammatory and autoimmune disease
Somatic mutations (also known as acquired mutations) are emerging as common, age-related processes that occur in all cells throughout the body. Somatic mutations are canonically linked to malignant processes but over the past decade have been increasingly causally connected to benign diseases including rheumatic conditions. Here we outline the contribution of somatic mutations to complex and monogenic immunological diseases with a detailed review of unique aspects associated with such causes. Somatic mutations can cause early- or late-onset rheumatic monogenic diseases but also contribute to the pathogenesis of complex inflammatory and immune-mediated diseases, affect disease progression and define new clinical subtypes. Although even variants with a low variant allele fraction can be pathogenic, clonal dynamics could lead to changes over time in the proportion of mutant cells, with possible phenotypic consequences for the individual. Thus, somatic mutagenesis and clonal expansion have relevant implications in genetic testing and counselling. On the basis of both increased recognition of somatic diseases in clinical practice and improved technical and bioinformatic processes, we hypothesize that there will be an ever-expanding list of somatic mutations in various genes leading to inflammatory conditions, particularly in late-onset disease. This Review discusses the involvement of early-stage and late-stage somatic mutations in the pathogenesis of both monogenic and multifactorial rheumatic diseases. The authors highlight new methods of detecting low-frequency variants and the implications for diagnosis and treatment in patients with rheumatic diseases.
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来源期刊
Nature Reviews Rheumatology
Nature Reviews Rheumatology 医学-风湿病学
CiteScore
29.90
自引率
0.90%
发文量
137
审稿时长
6-12 weeks
期刊介绍: Nature Reviews Rheumatology is part of the Nature Reviews portfolio of journals. The journal scope covers the entire spectrum of rheumatology research. We ensure that our articles are accessible to the widest possible audience.
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