Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
Eur J Immunol. 2022 May;52(5):705-716. doi: 10.1002/eji.202149210. Epub 2022 Apr 13.
Immune dysregulation polyendocrinopathy enteropathy X linked (IPEX) syndrome is an uncurable disease of the immune system, with immune dysregulation that is caused by mutations in FOXP3. Current treatment options, such as pharmacological immune suppression and allogeneic hematopoietic stem cell transplantation, have been beneficial but present limitations, and their life-long consequences are ill-defined. Other similar blood monogenic diseases have been successfully treated using gene transfer in autologous patient cells, thus providing an effective and less invasive therapeutic. Development of gene therapy for patients with IPEX is particularly challenging because successful strategies must restore the complex expression profile of the transcription factor FOXP3, ensuring it is tightly regulated and its cell subset-specific roles are maintained. This review summarizes current efforts toward achieving gene therapy to treat immune dysregulation in IPEX patients.
X 连锁免疫调节多内分泌腺病肠病相关(X 连锁多内分泌腺病肠病相关免疫失调)综合征是一种不可治愈的免疫系统疾病，由 FOXP3 基因突变引起。目前的治疗选择，如药物免疫抑制和同种异体造血干细胞移植，已经有一定的效果，但仍存在局限性，其长期后果也不明确。其他类似的血液单基因疾病已经成功地使用自体患者细胞中的基因转移进行治疗，从而提供了一种有效且侵袭性较小的治疗方法。为 IPEX 患者开发基因治疗特别具有挑战性，因为成功的策略必须恢复转录因子 FOXP3 的复杂表达谱，确保其受到严格调控，并维持其细胞亚群特异性作用。这篇综述总结了目前为治疗 IPEX 患者的免疫失调而进行基因治疗的努力。
