Infill Healthcare Communication, Königswinter, Germany.
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine at Charité University Hospital Berlin, Berlin, Germany.
Front Immunol. 2023 Jul 20;14:1208567. doi: 10.3389/fimmu.2023.1208567. eCollection 2023.
Activated PI3Kδ syndrome (APDS) is a rare inborn error of immunity (IEI) characterized primarily by frequent infections, lymphoproliferation and autoimmunity. Since its initial description in 2013, APDS has become part of the growing group of nearly 500 IEIs affecting various components of the immune system. The two subtypes of APDS - APDS1 and APDS2 - are caused by variants in the and genes, respectively. Due to the rarity of the disease and the heterogeneous clinical picture, many patients are not diagnosed until years after symptom onset. Another challenge is the large number of and variants whose functional significance for developing APDS is inconclusive. Treatment of APDS has so far been mostly symptom-oriented with immunoglobulin replacement therapy, immunosuppressive therapies and antibiotic or antiviral prophylaxes. Additionally, allogeneic stem cell transplantation as well as new targeted therapies are options targeting the root cause that may improve patients' quality of life and life expectancy. However, the clinical course of the disease is difficult to predict which complicates the choice of appropriate therapies. This review article discusses diagnostic procedures and current and future treatment options, and highlights the difficulties that physicians, patients and their caretakers face in managing this complex disease. This article is based on cohort studies, the German and US guidelines on the management of primary immunodeficiencies as well as on published experience with diagnosis and compiled treatment experience for APDS.
活化的 PI3Kδ 综合征 (APDS) 是一种罕见的先天性免疫缺陷病 (IEI)，主要表现为频繁感染、淋巴组织增生和自身免疫。自 2013 年首次描述以来，APDS 已成为影响免疫系统各种成分的近 500 种 IEI 不断增加的一组疾病之一。APDS 的两种亚型 - APDS1 和 APDS2 - 分别由 和 基因的变异引起。由于疾病的罕见性和临床表现的异质性，许多患者在症状出现多年后才被诊断出来。另一个挑战是存在大量的 和 变异，其对 APDS 发病的功能意义尚无定论。APDS 的治疗迄今主要是对症治疗，包括免疫球蛋白替代疗法、免疫抑制疗法和抗生素或抗病毒预防。此外，异基因造血干细胞移植以及新的靶向治疗也是针对根本原因的选择，可能会改善患者的生活质量和预期寿命。然而，疾病的临床过程难以预测，这使得选择适当的治疗方法变得复杂。本文讨论了诊断程序以及目前和未来的治疗选择，并强调了医生、患者及其护理人员在管理这种复杂疾病时所面临的困难。本文基于队列研究、德国和美国原发性免疫缺陷管理指南以及 APDS 的诊断经验和已编译的治疗经验。
