免疫反应阻碍了溶酶体贮积症的治疗。
Immune response hinders therapy for lysosomal storage diseases.
作者信息
Ponder Katherine P
机构信息
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
出版信息
J Clin Invest. 2008 Aug;118(8):2686-9. doi: 10.1172/JCI36521.
Abstract
Enzyme replacement therapy (ERT) for the lysosomal storage disease mucopolysaccharidosis I (MPS I) involves i.v. injection of alpha-l-iduronidase, which can be taken up by cells throughout the body. While a significant immune response to ERT has been shown in patients with MPS I, little is known about what effect anti-enzyme antibodies have on treatment efficacy. In this issue of the JCI, Dickson et al. demonstrate that anti-enzyme antibodies inhibit enzyme uptake and substantially limit the therapeutic efficacy of ERT in canines with MPS I (see the related article beginning on page 2868). Furthermore, the induction of immune tolerance--via oral delivery of cyclosporine A and azathioprine for two months at the time of initiation of ERT with recombinant human alpha-L-iduronidase--improved enzyme uptake in organs. Therefore, transient immunosuppression may enhance ERT for lysosomal storage diseases.
摘要
用于溶酶体贮积病黏多糖贮积症I型（MPS I）的酶替代疗法（ERT）涉及静脉注射α-L-艾杜糖醛酸酶，该酶可被全身细胞摄取。虽然已在MPS I患者中显示出对ERT的显著免疫反应，但对于抗酶抗体对治疗效果有何影响却知之甚少。在本期《临床研究杂志》中，迪克森等人证明抗酶抗体抑制酶摄取，并在很大程度上限制了ERT对患有MPS I的犬类的治疗效果（见第2868页开始的相关文章）。此外，在开始使用重组人α-L-艾杜糖醛酸酶进行ERT时，通过口服环孢素A和硫唑嘌呤两个月来诱导免疫耐受，可改善器官中的酶摄取。因此，短暂的免疫抑制可能会增强针对溶酶体贮积病的ERT效果。
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