Tetramolecular immune complexes are more efficient than IVIg to prevent antibody-dependent in vitro and in vivo phagocytosis of blood cells
Tetramolecular immune complexes are more efficient than IVIg to prevent antibody-dependent in vitro and in vivo phagocytosis of blood cells
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DOI：
10.1111/j.1365-2141.2004.05105.x
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发表时间：
2004-10-01
影响因子：
6.5
通讯作者：
St-Amour, I
中科院分区：
文献类型：
--
作者：
Bazin, R;Lemieux, R;St-Amour, I
静脉注射免疫球蛋白（IVIg）在体内具有免疫调节作用，广泛用于治疗自身免疫性疾病，如特发性血小板减少性紫癜（ITP）。IVIg可阻止ITP患者血小板清除的机制尚未完全了解，但已知需要低亲和力Fc γ受体（Fc γ R）的参与，其与单体免疫球蛋白G（IgG）的相互作用较差。鉴于低亲和力Fc γ R在ITP治疗中的重要性，我们假设体外产生的免疫复合物（IC）可以重现IVIg的作用。用鼠单克隆抗人IgG和人Fc片段制备了小尺寸四分子IC。比较了四分子IC和IVIg对调理血细胞吞噬功能的体外和体内抑制作用。获得的结果表明，四分子IC在体外防止调理红细胞的吞噬作用和血小板减少小鼠模型中血小板的清除方面比IVIg有效至少6倍。
Intravenous immunoglobulins (IVIg) have immunomodulatory effects in vivo and are widely used in the treatment of autoimmune diseases, such as idiopathic thrombocytopenic purpura (ITP). The mechanisms by which IVIg can prevent platelet clearance in ITP patients are not fully understood but are known to require the participation of low affinity Fcgamma receptors (FcgammaRs), which interact poorly with monomeric immunoglobulin G (IgG). Given the importance of low affinity FcgammaRs in the treatment of ITP, we hypothesized that immune complexes (IC) produced in vitro could reproduce the effects of IVIg. Small-size tetramolecular IC were prepared using mouse monoclonal anti-human IgG and human Fc fragments. The effects of tetramolecular IC and IVIg on the in vitro and in vivo inhibition of phagocytosis of opsonized blood cells were compared. The results obtained showed that tetramolecular IC were at least six times more efficient than IVIg to prevent phagocytosis of opsonized red blood cells in vitro, and clearance of platelets in the thrombocytopenic mouse model.