用重组IgG Fc概括静脉注射免疫球蛋白的抗炎活性。
Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc.
作者信息
Anthony Robert M, Nimmerjahn Falk, Ashline David J, Reinhold Vernon N, Paulson James C, Ravetch Jeffrey V
机构信息
Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY 10021, USA.
出版信息
Science. 2008 Apr 18;320(5874):373-6. doi: 10.1126/science.1154315.
It is well established that high doses of monomeric immunoglobulin G (IgG) purified from pooled human plasma [intravenous immunoglobulin (IVIG)] confer anti-inflammatory activity in a variety of autoimmune settings. However, exactly how those effects are mediated is not clear because of the heterogeneity of IVIG. Recent studies have demonstrated that the anti-inflammatory activity of IgG is completely dependent on sialylation of the N-linked glycan of the IgG Fc fragment. Here we determine the precise glycan requirements for this anti-inflammatory activity, allowing us to engineer an appropriate IgG1 Fc fragment, and thus generate a fully recombinant, sialylated IgG1 Fc with greatly enhanced potency. This therapeutic molecule precisely defines the biologically active component of IVIG and helps guide development of an IVIG replacement with improved activity and availability.
众所周知，从混合人血浆中纯化的高剂量单体免疫球蛋白G（IgG）[静脉注射免疫球蛋白（IVIG）]在多种自身免疫环境中具有抗炎活性。然而，由于IVIG的异质性，这些作用的确切介导方式尚不清楚。最近的研究表明，IgG的抗炎活性完全依赖于IgG Fc片段N-连接聚糖的唾液酸化。在这里，我们确定了这种抗炎活性所需的精确聚糖，从而能够设计出合适的IgG1 Fc片段，进而产生一种效力大大增强的完全重组的、唾液酸化的IgG1 Fc。这种治疗分子精确地定义了IVIG的生物活性成分，并有助于指导开发具有更高活性和可用性的IVIG替代品。
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