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首页> 外文期刊>The Journal of Clinical Investigation: The Official Journal of the American Society for Clinical Investigation >Oral immunotherapy tolerizes mice to enzyme replacement therapy for Morquio A syndrome
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Oral immunotherapy tolerizes mice to enzyme replacement therapy for Morquio A syndrome

机译:口服免疫疗法可耐受小鼠接受Morquio A综合征的酶替代疗法

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摘要

Immune response to therapeutic enzymes poses a detriment to patient safety and treatment outcome. Enzyme replacement therapy (ERT) is a standard therapeutic option for some types of mucopolysaccharidoses, including Morquio A syndrome caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency. Current protocols tolerize patients using cytotoxic immunosuppressives, which can cause adverse effects. Here we show development of tolerance in Morquio A mice via oral delivery of peptide or GALNS for 10 days prior to ERT. Our results show that using an immunodominant peptide (110) or the complete GALNS enzyme to orally induce tolerance to GALNS prior to ERT resulted in several improvements to ERT in mice: (a) decreased splenocyte proliferation after in vitro GALNS stimulation, (b) modulation of the cytokine secretion profile, (c) decrease in GALNS-specific IgG or IgE in plasma, (d) decreased GAG storage in liver, and (e) fewer circulating immune complexes in plasma. This model could be extrapolated to other lysosomal storage disorders in which immune response hinders ERT.
机译:对治疗性酶的免疫反应会损害患者的安全和治疗结果。酶替代疗法 (ERT) 是某些类型粘多糖添加物的标准治疗选择,包括由 N-乙酰半乳糖胺-6-硫酸酯酶 (GALNS) 缺乏引起的 Morquio A 综合征。目前的方案耐受使用细胞毒性免疫抑制剂的患者,这可能会引起不良反应。在这里,我们显示了Morquio A小鼠在ERT前10天通过口服肽或GALNS的耐受性发展。我们的结果表明,在ERT之前使用免疫显性肽(110)或完整的GALNS酶口服诱导对GALENS的耐受性导致小鼠ERT的几种改善:(a)体外GALNS刺激后脾细胞增殖减少,(b)细胞因子分泌谱的调节,(c)血浆中GALNS特异性IgG或IgE的降低, (d)肝脏中的GAG储存减少,以及(e)血浆中循环免疫复合物减少。该模型可以外推到其他溶酶体贮积症,其中免疫反应阻碍了 ERT。

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