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首页> 外文期刊>Molecular Immunology >Complement activation-related pseudoallergy: A stress reaction in blood triggered by nanomedicines and biologicals
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Complement activation-related pseudoallergy: A stress reaction in blood triggered by nanomedicines and biologicals

机译：补体激活相关的假性过敏：纳米药物和生物制剂引发的血液应激反应

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摘要

Intravenous injection of a variety of nanotechnology enhanced (liposomal, micellar, polymer-conjugated) and protein-based (antibodies, enzymes) drugs can lead to hypersensitivity reactions (HSRs), also known as infusion, or anaphylactoid reactions. The molecular mechanism of mild to severe allergy symptoms may differ from case to case and is mostly not known, however, in many cases a major cause, or contributing factor is activation of the complement (C) system. The clinical relevance of C activation-related HSRs, a non-IgE-mediated pseudoallergy (CARPA), lies in its unpredictability and occasional lethal outcome. Accordingly, there is an unmet medical need to develop laboratory assays and animal models that quantitate CARPA. This review provides basic information on CARPA; a short history, issues of nomenclature, incidence, classification of reactogenic drugs and symptoms, and the mechanisms of C activation via different pathways. It is pointed out that anaphylatoxin-induced mast cell release may not entirely explain the severe reactions; a "second hit" on allergy mediating cells may also contribute. In addressing the increasing requirements for CARPA testing, the review evaluates the available assays and animal models, and proposes a possible algorithm for the screening of reactogenic drugs and hypersensitive patients. Finally, an analogy is proposed between CARPA and the classic stress reaction, suggesting that CARPA represents a "blood stress" reaction, a systemic fight of the body against harmful biological and chemical agents via the anaphylatoxin/mast-cell/circulatory system axis, in analogy to the body's fight of physical and emotional stress via the hypothalamo/pituitary/adrenal axis. In both cases the response to a broad variety of noxious effects are funneled into a uniform pattern of physiological changes.
机译：静脉内注射各种增强的纳米技术（脂质体，胶束，聚合物结合的）和基于蛋白质的（抗体，酶）药物可导致超敏反应（HSR），也称为输液或类过敏反应。轻度至重度过敏症状的分子机制可能因情况而异，并且大多数情况尚不清楚，但是，在许多情况下，主要原因或促成因素是补体（C）系统的激活。 C活化相关的HSR（一种非IgE介导的拟变态反应（CARPA））的临床意义在于其不可预测性和偶发性致命结果。因此，开发定量化CARPA的实验室测定和动物模型的医疗需求尚未得到满足。这篇综述提供了关于CARPA的基本信息;历史短，命名问题，发生率，反应性药物和症状的分类以及通过不同途径激活C的机制。需要指出的是，过敏毒素诱导的肥大细胞释放可能不能完全解释严重的反应。过敏介导细胞的“第二击”也可能起作用。为了满足对CARPA测试日益增长的需求，该评价评估了可用的测定法和动物模型，并提出了一种筛选反应原性药物和过敏性患者的可能算法。最后，提出了CARPA与经典应激反应之间的类比，表明CARPA代表“血液应激”反应，即人体通过过敏毒素/肥大细胞/循环系统轴与有害生物化学物质的系统性斗争。类似于通过下丘脑/垂体/肾上腺轴对抗身体的生理和情绪压力。在这两种情况下，对各种有害作用的反应都汇聚成统一的生理变化模式。

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