Division of Immunology and Allergy, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
J Clin Immunol. 2017 Aug;37(6):582-591. doi: 10.1007/s10875-017-0421-7. Epub 2017 Jul 26.
Inherited defects in the adenosine deaminase (ADA) enzyme can cause severe combined immune deficiency (SCID) and systemic abnormalities. Management options for ADA-deficient patients include enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy (GT). Here, we describe the long-term benefits of these treatments.
Survival, infections, systemic sequelae, and laboratory assessments were recorded for all ADA-deficient SCID patients, managed at a single center since 1985, who survived 5 or more years following treatment.
Of 20 ADA-deficient patients, the 8 (40%) who survived 5 or more years (range 6-29.5 years, median 14 years) were included in the study. Among the long-term survivors, two patients were treated exclusively with ERT, five underwent HSCT (three from HLA-matched sibling donors, two from HLA-mismatched related donors), and one received GT. The long-term survivors often suffered from recurrent respiratory infections; however, opportunistic infections occurred in only one patient. Systemic sequelae included lung disease such as bronchiectasis and asthma (four patients), neurologic abnormalities (six patients), metabolic disturbances (two patients), allergy and autoimmunity (six patients), and neoplasms (three patients). Normal CD4 T cell numbers and function, as well as antibody production, were usually observed after HSCT and GT, but not after ERT. Late deaths occurred in two patients at 15 and 25 years after HSCT, respectively, and were attributed to respiratory failure.
ADA-deficient patients commonly suffer from long-term complications, emphasizing the need for improved management and for multi-disciplinary follow-up.
腺苷脱氨酶（ADA）酶的遗传缺陷可导致严重联合免疫缺陷（SCID）和全身性异常。ADA 缺陷患者的治疗选择包括酶替代疗法（ERT）、造血干细胞移植（HSCT）和基因治疗（GT）。在这里，我们描述了这些治疗方法的长期益处。
记录了自 1985 年以来在单一中心接受治疗且存活 5 年以上的所有 ADA 缺陷性 SCID 患者的生存情况、感染、全身后遗症和实验室评估。
在 20 名 ADA 缺陷患者中，有 8 名（40%）存活 5 年以上（范围 6-29.5 岁，中位数 14 岁）的患者被纳入研究。在长期幸存者中，有 2 名患者仅接受 ERT 治疗，5 名患者接受 HSCT（3 名来自 HLA 匹配的同胞供者，2 名来自 HLA 不匹配的相关供者），1 名患者接受 GT 治疗。长期幸存者经常患有复发性呼吸道感染；然而，仅 1 名患者发生机会性感染。全身后遗症包括支气管扩张和哮喘等肺部疾病（4 名患者）、神经异常（6 名患者）、代谢紊乱（2 名患者）、过敏和自身免疫（6 名患者）和肿瘤（3 名患者）。HSCT 和 GT 后通常会观察到 CD4 T 细胞数量和功能以及抗体产生正常，但 ERT 后则不然。2 名患者分别在 HSCT 后 15 年和 25 年死于晚期，死因分别为呼吸衰竭。
ADA 缺陷患者常患有长期并发症，强调需要改进管理和多学科随访。
