Department of Pediatrics, University of California, Irvine, CA, USA.
Department of Pediatrics, University of Washington and Seattle Children's Research Institute Seattle, Seattle, WA, USA.
Expert Rev Clin Immunol. 2022 Jun;18(6):609-623. doi: 10.1080/1744666X.2022.2074400. Epub 2022 May 19.
Wiskott-Aldrich syndrome (WAS) serves as the prototype of how variants in a gene, which encodes a protein central to actin cytoskeletal homeostasis can manifest clinically in a variety of ways including infection, atopy, autoimmunity, inflammation, bleeding, neutropenia, non-malignant lymphoproliferation, and malignancy. Despite the discovery of the gene almost 30 years ago, our understanding of the pathophysiological mechanisms underlying WAS continues to unfold.
This review will provide an overview of the approach to the diagnosis of WAS as well as the management of its associated complications. Advances in the use of allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy as well as the associated challenges unique to WAS will be discussed.
Basic research, combined with clinical research focusing on longitudinal analysis of WAS patients, will help clarify determinants that influence WAS pathogenesis as well as clinical complications and outcomes. Advances in curative approaches including the use of alternative donor HSCT for WAS continue to evolve. Gene therapy employing safer and more effective protocols ensuring full correction of WAS will provide life-saving benefit to WAS patients who are unable to undergo HSCT.
Wiskott-Aldrich 综合征（WAS）是基因变异如何以多种方式在临床上表现的原型，包括感染、特应性、自身免疫、炎症、出血、中性粒细胞减少、非恶性淋巴增生和恶性肿瘤。尽管近 30 年前发现了 基因，但我们对 WAS 潜在病理生理机制的理解仍在不断发展。
本篇综述将概述 WAS 的诊断方法以及其相关并发症的治疗管理。讨论了同种异体造血干细胞移植（HSCT）和基因治疗的进展，以及 WAS 特有的相关挑战。
基础研究与临床研究相结合，专注于对 WAS 患者的纵向分析，将有助于阐明影响 WAS 发病机制以及临床并发症和结果的决定因素。包括使用替代供体 HSCT 治疗 WAS 的根治方法的进展仍在不断发展。采用更安全、更有效的方案进行基因治疗，确保 WAS 完全纠正，将为无法接受 HSCT 的 WAS 患者提供救命的益处。
