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首页> 外文期刊>International journal of clinical pharmacology and therapeutics >Perspectives from B cell immunology: fact and fancy
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Perspectives from B cell immunology: fact and fancy

机译：B细胞免疫学的观点：事实与幻想

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In this article, the formation of antibodies during enzyme replacement therapy (ERT) for lysosomal storage diseases (LSDs) is reviewed in the light of present-day immunological concepts of immunogenicity and tolerance. Except in Gaudier disease, anti-enzyme antibodies frequently form (mainly im-munoglobulin G) in patients receiving ERT, though they tend to wane as treatment continues. If the therapeutic enzyme is inhibited by antibodies, no significant modification to treatment is normally warranted, in clear contrast to therapy of hemophilia with clotting factors. The main adverse consequences of ERT, observed in only some patients, are sporadic hypersensitivity reactions, which are likely to be humorally mediated. Some infusion-related reactions are probably due to antibodies. In order to minimize immunogenicity, infused enzymes should be deaggregated and administered at low doses. In addition, inadvertent exposure to co-stimuli that might activate antigen-specific T or B lymphocytes should be avoided. The presence of cross-reacting immunological material, such as in patients with low levels or missense mutations of a gene coding for a lysosomal enzyme, tends to correlate with immune tolerance to the administered enzyme. There is a need for reliable biomarkers for therapeutic efficacy: some directions for further exploration are suggested. In animal models of LSDs, gene therapy delivered via viral vectors can rectify the lysosomal defect, and regulatory T cells that suppress antibody formation can be induced. This is a promising strategy that warrants further investigation in patients with LSDs.simon.hunt@path.ox.ac.uk
机译：在本文中，根据当今免疫原性和耐受性的免疫学概念，综述了溶酶体贮积病（LSD）的酶替代疗法（ERT）期间抗体的形成。除高迪氏病外，接受ERT的患者经常会形成抗酶抗体（主要是免疫球蛋白G），尽管随着治疗的继续它们会逐渐消失。如果治疗性酶被抗体抑制，则通常不需对治疗进行重大修改，这与用凝血因子治疗血友病形成鲜明对比。仅在部分患者中观察到ERT的主要不良后果是偶发的超敏反应，这很可能是通过体液介导的。一些与输注相关的反应可能是由于抗体引起的。为了使免疫原性最小化，应分解注入的酶并以低剂量给药。此外，应避免无意中暴露于可能激活抗原特异性T或B淋巴细胞的共刺激物。交叉反应免疫物质的存在，例如在具有低水平或编码溶酶体酶的基因的错义突变的患者中，往往与对所施用酶的免疫耐受性相关。对于治疗功效，需要可靠的生物标记物：建议进一步探索的一些方向。在LSD的动物模型中，通过病毒载体进行的基因治疗可以纠正溶酶体缺陷，并且可以诱导抑制抗体形成的调节性T细胞。这是一种有前途的策略，值得对LSDs.simon.hunt@path.ox.ac.uk的患者进行进一步调查

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