Long-term efficacy of enzyme replacement therapy for Adenosine deaminase (ADA)-deficient Severe Combined Immunodeficiency (SCID)
Long-term efficacy of enzyme replacement therapy for Adenosine deaminase (ADA)-deficient Severe Combined Immunodeficiency (SCID)
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DOI：
10.1016/j.clim.2005.07.006
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发表时间：
2005-11-01
影响因子：
8.6
通讯作者：
Kohn, DB
中科院分区：
文献类型：
--
作者：
Chan, B;Wara, D;Kohn, DB
腺苷脱氨酶（ADA）缺陷型重症联合免疫缺陷症（ADA缺陷型SCID）的特征是腺苷代谢缺陷导致淋巴细胞发育和功能受损。聚乙二醇结合腺苷脱氨酶（PEG-ADA）的酶替代疗法可最大限度地减少未接受骨髓移植的ADA缺陷患者的感染并发症。在PEG-ADA治疗中，具有酶活性的ADA持续循环以充当代谢库，对在不存在ADA的情况下积累至高水平的腺苷和脱氧腺苷代谢物进行解毒。研究表明，在开始PEG-ADA治疗后，循环T和B淋巴细胞和NK细胞的绝对数量增加，并产生保护性免疫功能。但长期疗效尚不清楚。这项回顾性研究旨在评估PEG-ADA治疗的长期有效性，基于对过去十年中接受治疗的9名ADA缺陷型SCID患者（5 - 15岁）的免疫功能的评估。结果显示，所有接受PEG-ADA治疗的患者的淋巴细胞计数始终低于正常范围，尽管最初有所改善。有丝分裂增殖反应在治疗几年后逐渐下降，正常的抗原反应比预期的要少。到目前为止，这些低数量和功能的淋巴细胞已经足以提供保护性免疫。这些患者应密切随访，以检测在未来几十年的PEG-ADA治疗中免疫功能随衰老而过早下降。(c)2005年爱思唯尔公司All rights reserved.
Adenosine deaminase (ADA)-deficient Severe Combined Immunodeficiency (ADA-deficient SCID) is characterized by impaired lymphocyte development and function resulting from the adenosine metabolism defect. Enzyme replacement therapy with polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) minimizes infectious complications of ADA-deficient patients who have not received bone marrow transplantation. In PEG-ADA therapy, enzymatically active ADA continuously circulates to act as a metabolic sink, detoxifying the adenosine and deoxyadenosine metabolites that accumulate to high levels in the absence of ADA. Studies have shown that upon the initiation of PEG-ADA therapy, the absolute numbers of circulating T and B lymphocytes and NK cells increase and protective immune function develops. However, the long-term efficacy is unknown. This retrospective study was designed to assess the long-term effectiveness of PEG-ADA treatment, based on evaluation of the immune function of nine ADA-deficient SCID patients (age 5-15) treated over the past decade. The results showed that the lymphocyte counts of all of the PEG-ADA treated patients were below the normal range at all times, despite initial improvements. A gradual decline of mitogenic proliferative responses occurred after a few years of treatment and normal antigenic response occurred less than expected. To this date, these low numbers and functions of lymphocytes had been adequate to provide protective immunity. These patients should be followed closely to detect a premature decline in immune function with aging in future decades of PEG-ADA therapy. (c) 2005 Elsevier Inc. All rights reserved.