Primary immune regulatory disorders: a growing universe of immune dysregulation.
Primary immune regulatory disorders: a growing universe of immune dysregulation.
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DOI：
10.1097/aci.0000000000000689
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发表时间：
2020-12
影响因子：
2.8
通讯作者：
Torgerson TR
中科院分区：
文献类型：
--
作者：
Chan AY;Torgerson TR
原发性免疫调节障碍（PIRD）是一种不断增长的疾病子集，称为先天性免疫缺陷。与典型的原发性免疫缺陷疾病（通常表现为严重、复发或不寻常的感染）不同，PIRD的临床表现主要由免疫介导的病理学（自身免疫、自身炎症/炎症过度、淋巴细胞增殖、恶性肿瘤和严重特应性）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正在迅速增长。已鉴定的基因通常编码在调节对各种触发物的免疫反应中起关键作用的蛋白质。了解PIRD潜在的分子机制有助于阐明临床表型，并有助于确定靶向治疗。在某些情况下，造血细胞移植（HCT）已成功地用作治愈。重要的是要认识到广泛的临床表现PIRD患者可能有典型的“免疫缺陷”的非典型症状。由于其不同的免疫失调问题，他们往往主要由其他亚专家管理。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。反过来，这可以在指导临床管理，选择有效的治疗方法和决定HCT的适当性方面发挥重要作用。
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 pathology (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.