Activation of cryptic IgG reactive with BAFF, amyloid beta peptide and GM-CSF during the industrial fractionation of human plasma into therapeutic intravenous immunoglobulins
Activation of cryptic IgG reactive with BAFF, amyloid beta peptide and GM-CSF during the industrial fractionation of human plasma into therapeutic intravenous immunoglobulins
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DOI：
10.1016/j.clim.2009.06.005
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发表时间：
2009-10-01
影响因子：
8.6
通讯作者：
Lemieux, Real
中科院分区：
文献类型：
--
作者：
St-Amour, Isabelle;Laroche, Andre;Lemieux, Real
IVIg在大多数自身免疫性和炎症性疾病中的治疗作用机制仍不清楚。IVIg已显示与多种人类蛋白质结合，包括BAFF、淀粉样β肽和GM-CSF。已经表明，这种自身反应性可能有助于IVIg的治疗性免疫调节作用。在这项工作中，我们表明，在非变性条件下从血浆中纯化的天然IgG比IVIg的自身反应性低得多。然而，在工业血浆分离过程中使用的轻微变性条件下，通过短暂孵育，天然IgG与BAFF、淀粉样β肽和GM-CSF的自身反应性显著增加。我们的结论是，工业血浆分离中使用的相对温和的条件足以变性，以激活大量的隐匿性自身反应性血浆IgG，这可能不仅涉及IVIg的治疗性免疫调节作用，而且还涉及在IVIg输注患者中经常观察到的不良“过敏”反应。(C)2009 Elsevier Inc. All rights reserved.
The mechanisms of therapeutic action of IVIg are still unclear inmost autoimmune and inflammatory diseases. IVIg have been shown to bind to a variety of human proteins including BAFF, amyloid beta peptide and GM-CSF. It has been suggested that this autoreactivity could contribute to the therapeutic immunomodulatory effects of IVIg. In this work, we showed that native IgG purified from plasma under non-denaturing conditions were much less autoreactive than IVIg. However the native IgG autoreactivity with BAFF, amyloid beta peptide and GM-CSF was significantly increased by short incubation under the slightly denaturing conditions used during industrial plasma fractionation. We conclude that the relatively mild conditions used in industrial plasma fractionation are sufficiently denaturing to activate a significant amount of cryptic autoreactive plasma IgG which could be involved not only in the therapeutic immunomodulatory effects of IVIg but also in the adverse "allergic" reactions often observed in IVIg-infused patients. (C) 2009 Elsevier Inc. All rights reserved.