The carbohydrate switch between pathogenic and immunosuppressive antigen-specific antibodies
The carbohydrate switch between pathogenic and immunosuppressive antigen-specific antibodies
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DOI：
10.1111/exd.12171
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发表时间：
2013-08-01
影响因子：
3.6
通讯作者：
Ehlers, Marc
中科院分区：
文献类型：
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作者：
Collin, Mattias;Ehlers, Marc
IgG抗体在其每个恒定重链区中的Asn 297处具有一个保守的N-糖基化位点。这些Fc聚糖影响IgG抗体的整体结构和促炎或抗炎效应子功能。由四个N-乙酰基-葡糖胺（GlcNAc）和三个甘露糖残基组成的双触角核心聚糖结构可以进一步用岩藻糖、二等分GlcNAc和末端半乳糖或半乳糖加唾液酸修饰。长期以来，非半乳糖基化（无半乳糖基化; G 0）IgG抗体与类风湿性关节炎（RA）自身免疫患者的促炎效应子功能相关。相比之下，已经显示唾液酸化IgG负责静脉内免疫球蛋白（IVIG;从合并的人血浆中纯化的IgG）的抗炎作用，静脉内免疫球蛋白以高剂量（2g/kg）施用用于自身免疫患者的全身治疗。越来越明显的是，促炎性免疫应答，如自身免疫反应，主要诱导抗原特异性G 0 IgG，而耐受性诱导免疫抑制性半乳糖基化和唾液酸化IgG。在生理条件下，差异糖基化的IgG以抗原特异性方式作为免疫复合物（IC）介导其促炎或抗炎效应子功能。因此，抗原特异性半乳糖基化和唾液酸化IgG可能是一种有前途的治疗工具，用于在自身免疫性或过敏性患者中重建对确定的（自身）抗原的耐受性。在这里，我们总结了这些发现，并概述了我们对差异糖基化抗原特异性IgG抗体的发展和功能的观点。
IgG antibodies have one conserved N-glycosylation site at Asn 297 in each of their constant heavy chain regions. These Fc glycans influence the overall structure and pro- or anti-inflammatory effector functions of IgG antibodies. The biantennary core glycan structure, consisting of four N-acetyl-glucosamine (GlcNAc) and three mannose residues, can be further decorated with fucose, a bisecting GlcNAc and terminal galactose or galactose plus sialic acid. Non-galactosylated (agalactosylated; G0) IgG antibodies have long been associated with pro-inflammatory effector functions in autoimmune patients with rheumatoid arthritis (RA). In contrast, it has been shown that sialylated IgGs are responsible for anti-inflammatory effects of intravenous immunoglobulin (IVIG; purified IgG from pooled human plasma), which is administered at high doses (2g/kg) for the systemic treatment of autoimmune patients. It has become increasingly evident that pro-inflammatory immune responses, such as autoimmune reactions, primarily induce antigen-specific G0 IgGs, whereas tolerance induces immunosuppressive galactosylated and sialylated IgGs. Under physiological conditions, differentially glycosylated IgGs mediate their pro- or anti-inflammatory effector functions obviously as immune complexes (IC) in an antigen-specific manner. Therefore, antigen-specific galactosylated and sialylated IgGs may be a promising therapeutic tool for re-establishing tolerance against defined (self-) antigens in autoimmune or allergic patients. Here, we summarize these findings and outline our viewpoint on the development and function of differentially glycosylated antigen-specific IgG antibodies.