自身炎症和自身免疫性疾病的体细胞突变
Somatic mutations in autoinflammatory and autoimmune disease
影响因子:32.70000
分区:医学1区 Top / 风湿病学1区
发表日期:2024 Nov
作者:
Sofia Torreggiani, Flore S Castellan, Ivona Aksentijevich, David B Beck
摘要
体细胞突变（也称为获得的突变）已成为常见的，与年龄相关的过程，这些过程发生在整个体内的所有细胞中。体细胞突变与恶性过程有关，但在过去的十年中，与包括风湿病在内的良性疾病有因果关系越来越多。在这里，我们概述了体细胞突变对复杂和单基因免疫疾病的贡献，对与此类原因相关的独特方面进行了详细评论。体细胞突变会引起早期或晚期的风湿性单基因疾病，但也有助于复杂的炎症和免疫介导的疾病的发病机理，影响疾病进展并定义新的临床亚型。尽管即使是具有较低变体等位基因分数的变体也可能是致病性的，但克隆动力学也可能导致突变细胞比例随时间变化，对个体可能会产生表型后果。因此，体细胞诱变和克隆扩张在基因检测和咨询中具有相关的意义。在临床实践中对体细胞疾病的识别以及改善的技术和生物信息学过程的基础上，我们假设在各种基因中会有不断扩展的体细胞突变清单，导致炎症状况，尤其是在晚期疾病中。
Abstract
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.