Division of Pediatric Allergy, Immunology, and BMT.
Division of Pediatric Rheumatology, Department of Pediatrics, University of California, San Francisco, San Francisco, California.
Curr Opin Allergy Clin Immunol. 2020 Dec;20(6):582-590. doi: 10.1097/ACI.0000000000000689.
Primary immune regulatory disorders (PIRD) are a growing subset of diseases referred to as inborn errors of immunity. Unlike classical primary immune deficiency disorders that typically present with severe, recurrent, or unusual infections, the clinical manifestations of PIRD are dominated by immune-mediated diseases (autoimmunity, autoinflammation/hyperinflammation, lymphoproliferation, malignancy, and severe atopy). This review introduces the concept of PIRD including clinical phenotypes, treatments, and new PIRD-associated gene defects.
The number of genetic defects associated with PIRD is rapidly growing. The identified genes often encode proteins that play critical roles in regulating the immune response to various triggers. Understanding the molecular mechanisms underlying PIRD has shed light on the clinical phenotypes and has helped to identify targeted therapies. In some cases, hematopoietic cell transplant (HCT) has been successfully employed as a cure.
It is important to recognize the broad clinical manifestations of PIRD as patients may have symptoms atypical of classical 'immunodeficiency'. Because of their diverse immune dysregulation problems, they are often primarily managed by other subspecialists. Immunologists can help connect the diverse immune-mediated pathologies to a gene defect. This, in turn, can play a significant role in directing clinical management, selecting effective therapy, and deciding on appropriateness of HCT.
原发性免疫调节紊乱（PIRD）是一类不断增多的疾病，被称为先天性免疫缺陷。与通常以严重、反复或不寻常感染为特征的经典原发性免疫缺陷不同，PIRD 的临床表现主要由免疫介导的疾病（自身免疫、自身炎症/过度炎症、淋巴增生、恶性肿瘤和严重过敏）主导。本文介绍了 PIRD 的概念，包括临床表型、治疗方法和新的 PIRD 相关基因缺陷。
与 PIRD 相关的遗传缺陷数量迅速增加。已鉴定的基因通常编码在调节对各种触发因素的免疫反应中起关键作用的蛋白质。对 PIRD 发病机制的理解揭示了其临床表型，并有助于确定靶向治疗方法。在某些情况下，造血细胞移植（HCT）已成功用作治疗方法。
认识到 PIRD 的广泛临床表现很重要，因为患者可能有非典型的经典“免疫缺陷”症状。由于其免疫失调问题多种多样，它们通常主要由其他专科医生管理。免疫学家可以帮助将不同的免疫介导的病理与基因缺陷联系起来。这反过来又可以在指导临床管理、选择有效治疗方法以及决定是否适合进行 HCT 方面发挥重要作用。
