人类先天性免疫错误 (IEI) 包括一组由损害先天性和适应性免疫的分子变异引起的疾病。 IEI 患者的临床特征主要是对一系列传染病的易感性，以及通常在儿童时期出现的自身免疫、自身炎症、过敏和恶性表型，通常在儿童时期做出诊断。然而，一些 IEI 患者由于疾病的症状延迟或其他原因而无法进行分子研究，因此在成年后才被发现。新一代测序 (NGS) 作为诊断技术的应用不断增加对 IEI 单基因原因的识别，从而提高诊断率并促进个性化治疗的可能性。这项工作是对 2005 年至 2023 年间 173 名疑似 IEI 的成年人进行的回顾性研究。Sanger、靶向基因组和全外显子组测序用于分子诊断。 173 名患者中有 44 名 (25.43%) 发现了致病变异。这44例患者的临床表型大多与感染易感性相关（63.64%）。当将接受分子诊断的队列与未接受分子诊断的队列进行比较时，发现免疫失调疾病的丰富程度。国际免疫学会联盟专家委员会 (IUIS) 第 4 组免疫失调疾病在这些成年患者中最为普遍。免疫失调作为杰弗里模型基金会成人警告信号中的一个新项目，显着提高了识别具有产生 IEI 的分子缺陷的患者的敏感性。© 2024。作者。

Human inborn errors of immunity (IEI) comprise a group of diseases resulting from molecular variants that compromise innate and adaptive immunity. Clinical features of IEI patients are dominated by susceptibility to a spectrum of infectious diseases, as well as autoimmune, autoinflammatory, allergic, and malignant phenotypes that usually appear in childhood, which is when the diagnosis is typically made. However, some IEI patients are identified in adulthood due to symptomatic delay of the disease or other reasons that prevent the request for a molecular study. The application of next-generation sequencing (NGS) as a diagnostic technique has given rise to an ever-increasing identification of IEI-monogenic causes, thus improving the diagnostic yield and facilitating the possibility of personalized treatment. This work was a retrospective study of 173 adults with IEI suspicion that were sequenced between 2005 and 2023. Sanger, targeted gene-panel, and whole exome sequencing were used for molecular diagnosis. Disease-causing variants were identified in 44 of 173 (25.43%) patients. The clinical phenotype of these 44 patients was mostly related to infection susceptibility (63.64%). An enrichment of immune dysregulation diseases was found when cohorts with molecular diagnosis were compared to those without. Immune dysregulation disorders, group 4 from the International Union of Immunological Societies Expert Committee (IUIS), were the most prevalent among these adult patients. Immune dysregulation as a new item in the Jeffrey Model Foundation warning signs for adults significantly increases the sensitivity for the identification of patients with an IEI-producing molecular defect.© 2024. The Author(s).