PDF(Pubmed)
Abstract：
Primary immune regulatory disorders (PIRDs) are inborn errors of immunity caused by a loss in the regulatory mechanism of the inflammatory or immune response, leading to impaired immunological tolerance or an exuberant inflammatory response to various stimuli due to loss or gain of function mutations. Whilst PIRDs may feature susceptibility to recurrent, severe, or opportunistic infection in their phenotype, this group of syndromes has broadened the spectrum of disease caused by defects in immunity-related genes to include autoimmunity, autoinflammation, lymphoproliferation, malignancy, and allergy; increasing focus on PIRDs has thus redefined the classical \'primary immunodeficiency\' as one aspect of an overarching group of inborn errors of immunity. The growing number of genetic defects associated with PIRDs has expanded our understanding of immune tolerance mechanisms and prompted identification of molecular targets for therapy. However, PIRDs remain difficult to recognize due to incomplete penetrance of their diverse phenotype, which may cross organ systems and present to multiple clinical specialists prior to review by an immunologist. Control of immune dysregulation with immunosuppressive therapies must be balanced against the enhanced infective risk posed by the underlying defect and accumulated end-organ damage, posing a challenge to clinicians. Whilst allogeneic hematopoietic stem cell transplantation may correct the underlying immune defect, identification of appropriate patients and timing of transplant is difficult. The relatively recent description of many PIRDs and rarity of individual genetic entities that comprise this group means data on natural history, clinical progression, and treatment are limited, and so international collaboration will be needed to better delineate phenotypes and the impact of existing and potential therapies. This review explores pathophysiology, clinical features, current therapeutic strategies for PIRDs including cellular platforms, and future directions for research.
摘要：
原发性免疫调节障碍（PIRD）是由炎症或免疫反应的调节机制丧失引起的先天性免疫错误，由于功能突变的丧失或获得，导致免疫耐受受损或对各种刺激产生强烈的炎症反应。虽然PIRD可能具有反复发作的易感性，严重,或表型中的机会性感染，这组综合征扩大了由免疫相关基因缺陷引起的疾病谱，包括自身免疫，自身炎症,淋巴增生,恶性肿瘤，和过敏；因此，对PIRD的日益关注已将经典的“原发性免疫缺陷”重新定义为先天免疫错误的总体组的一个方面。与PIRD相关的越来越多的遗传缺陷扩大了我们对免疫耐受机制的理解，并促进了对治疗分子靶标的识别。然而,由于其不同表型的不完全外显率，PIRD仍然难以识别，它可以跨器官系统，并在免疫学家审查之前呈现给多个临床专家。免疫抑制疗法对免疫失调的控制必须与潜在缺陷和累积的终末器官损伤引起的感染风险增加相平衡。对临床医生构成挑战。虽然异基因造血干细胞移植可以纠正潜在的免疫缺陷，确定合适的患者和移植时机是困难的。对许多PIRD的相对较新的描述和构成该组的个体遗传实体的稀有性意味着自然史上的数据，临床进展,治疗是有限的，因此，需要国际合作来更好地描述表型以及现有和潜在疗法的影响。这篇综述探讨了病理生理学，临床特征,目前PIRD的治疗策略，包括细胞平台，以及未来的研究方向。
