Sydney Children's Hospital, Randwick, NSW, Australia; Western Sydney University, Penrith, NSW, Australia.
Sydney Children's Hospital, Randwick, NSW, Australia; The School of Women's & Children's Health, University of New South Wales, Randwick, NSW, Australia.
J Allergy Clin Immunol Pract. 2023 Jun;11(6):1602-1622. doi: 10.1016/j.jaip.2023.04.018. Epub 2023 Apr 28.
Autoimmunity may be a manifestation of inborn errors of immunity, specifically as part of the subgroup of primary immunodeficiency known as primary immune regulatory disorders. However, although making a single gene diagnosis can have important implications for prognosis and management, picking patients to screen can be difficult, against a background of a high prevalence of autoimmune disease in the population. This review compares the genetics of common polygenic and rare monogenic autoimmunity, and explores the molecular mechanisms, phenotypes, and inheritance of autoimmunity associated with primary immune regulatory disorders, highlighting the emerging importance of gain-of-function and non-germline somatic mutations. A novel framework for identifying rare monogenic cases of common diseases in children is presented, highlighting important clinical and immunologic features that favor single gene disease and guides clinicians in selecting appropriate patients for genomic screening. In addition, there will be a review of autoimmunity in non-genetically defined primary immunodeficiency such as common variable immunodeficiency, and of instances where primary autoimmunity can result in clinical phenocopies of inborn errors of immunity.
自身免疫可能是先天性免疫缺陷的表现，特别是作为原发性免疫调节障碍这一原发性免疫缺陷亚组的一部分。然而，尽管进行单一基因诊断对预后和管理具有重要意义，但在人群中自身免疫性疾病高发的背景下，筛选患者可能具有一定难度。本综述比较了常见多基因和罕见单基因自身免疫的遗传学，并探讨了与原发性免疫调节障碍相关的自身免疫的分子机制、表型和遗传，强调了获得性功能和非种系体细胞突变的重要性。提出了一种用于鉴定儿童常见疾病中罕见单基因病例的新框架，强调了有利于单基因疾病的重要临床和免疫学特征，并指导临床医生选择适当的患者进行基因组筛查。此外，还将对非遗传性定义的原发性免疫缺陷（如常见可变免疫缺陷）中的自身免疫和原发性自身免疫导致先天性免疫缺陷临床表型模拟的情况进行综述。
