Kohn Donald B, Gaspar H Bobby
Departments of Microbiology, Immunology & Molecular Genetics; Pediatrics; and Molecular and Medical Pharmacology, University of California, Los Angeles, 3163 Terasaki Life Science Bldg., 610 Charles E. Young Drive East, Los Angeles, CA, 90095, USA.
Molecular and Cellular Immunology Section, UCL Institute of Child Health, University College London, London, UK.
J Clin Immunol. 2017 May;37(4):351-356. doi: 10.1007/s10875-017-0373-y. Epub 2017 Feb 14.
Adenosine deaminase-deficient severe combined immune deficiency (ADA SCID) accounts for 10-15% of cases of human SCID. From what was once a uniformly fatal disease, the prognosis for infants with ADA SCID has improved greatly based on the development of multiple therapeutic options, coupled with more frequent early diagnosis due to implementation of newborn screening for SCID. We review the various treatment approaches for ADA SCID including allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched sibling or family member or from a matched unrelated donor or a haplo-identical donor, autologous HSCT with gene correction of the hematopoietic stem cells (gene therapy-GT), and enzyme replacement therapy (ERT) with polyethylene glycol-conjugated adenosine deaminase. Based on growing evidence of safety and efficacy from GT, we propose a treatment algorithm for patients with ADA SCID that recommends HSCT from a matched family donor, when available, as a first choice, followed by GT as the next option, with allogeneic HSCT from an unrelated or haplo-identical donor or long-term ERT as other options.
腺苷脱氨酶缺乏的重症联合免疫缺陷（ADA SCID）占人类SCID病例的10-15%。曾经是一种普遍致命的疾病，由于多种治疗选择的发展，以及因实施SCID新生儿筛查而更频繁地进行早期诊断，ADA SCID婴儿的预后有了很大改善。我们回顾了ADA SCID的各种治疗方法，包括来自人类白细胞抗原匹配的同胞或家庭成员、匹配的无关供体或单倍体相合供体的异基因造血干细胞移植（HSCT），对造血干细胞进行基因校正的自体HSCT（基因治疗-GT），以及聚乙二醇共轭腺苷脱氨酶的酶替代疗法（ERT）。基于GT越来越多的安全性和有效性证据，我们提出了一种针对ADA SCID患者的治疗方案，建议在有匹配的家庭供体时，首选其进行HSCT，其次是GT作为下一个选择，来自无关或单倍体相合供体的异基因HSCT或长期ERT作为其他选择。
