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静脉注射用免疫球蛋白(IVIg)中的二聚 IgG 复合物不能诱导体外中性粒细胞脱颗粒或补体激活。

Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation.

机构信息

Department of Immunopathology, Sanquin Blood Supply and Landsteiner laboratory Amsterdam Medical Centre, University of Amsterdam, CX, Amsterdam, the Netherlands.

Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Acedemic Centre of Drug Research (LACDR), Leiden, the Netherlands.

出版信息

PLoS One. 2018 Apr 10;13(4):e0195729. doi: 10.1371/journal.pone.0195729. eCollection 2018.

Abstract

PURPOSE

Intravenous immunoglobulin (IVIg) products contain various amounts of dimeric IgG complexes. Current insights into the possible biological activities of these dimers remain controversial, and both immunemodulating and immune-activating effects have been reported. Here, we analyzed the putative immune-activating effects of dimers isolated from IVIg.

METHODS

Dimers isolated from IVIg were purified by high-performance size-exclusion chromatography (HP-SEC) and tested for the ability to induce neutrophil degranulation in vitro.

RESULTS

Dimers isolated from IVIg were found to be incapable of inducing in vitro neutrophil degranulation or complement activation, even at concentrations exceeding those expected to be reached upon administration in patients. These results depend on the removal of artefactual activation by using 0.1 micron filtration and the use of poloxamer to prevent adsorption of IgG onto the solid phase.

CONCLUSIONS

The data suggest dimeric IgG found in IVIg may bind to Fc-receptors without causing activation.

摘要

目的

静脉注射免疫球蛋白 (IVIg) 产品含有不同量的二聚体 IgG 复合物。目前对这些二聚体可能具有的生物学活性的认识仍存在争议,有报道称其具有免疫调节和免疫激活作用。在这里,我们分析了从 IVIg 中分离出的二聚体的潜在免疫激活作用。

方法

通过高效体积排阻色谱 (HP-SEC) 从 IVIg 中分离出二聚体,并测试其在体外诱导嗜中性粒细胞脱颗粒的能力。

结果

从 IVIg 中分离出的二聚体被发现不能诱导体外嗜中性粒细胞脱颗粒或补体激活,即使在浓度超过患者给药时预期达到的浓度时也是如此。这些结果取决于通过使用 0.1 微米过滤去除人为激活,以及使用泊洛沙姆防止 IgG 吸附到固相上。

结论

数据表明,IVIg 中发现的二聚体 IgG 可能与 Fc 受体结合而不引起激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afae/5892932/9d18c8382aad/pone.0195729.g001.jpg

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