Institut National de la Sante et de la Recherche Medicale Unité 1138, Paris, France; Centre de Recherche des Cordeliers, Equipe 16-Immunopathology and therapeutic immunointervention, Université Pierre et Marie Curie - Paris, Paris, France.
Eur J Immunol. 2014 Jul;44(7):2059-63. doi: 10.1002/eji.201444440. Epub 2014 May 2.
Several mechanisms account for the beneficial effect of intravenous immunoglobulin (IVIg) in autoimmune and inflammatory diseases. These mechanisms include effects on the cellular compartment and on the humoral compartment. Thus, IVIg impacts on dendritic cells, macrophages, neutrophils, basophils, NK cells, and B and T lymphocytes. Several studies have emphasized that the antiinflammatory effect of IVIg is dependent on α2,6-sialylation of the N-linked glycan on asparagine-297 of the Fc portion of IgG. However, recent reports have questioned the necessity of sialylated Fc and the role of FcγRIIB in IVIg-mediated antiinflammatory effects. In view of the critical role played by Th17 cells in several autoimmune pathologies and the increasing use of IVIg in several of these conditions, by using neuraminidase-treated, desialylated IVIg, we addressed whether the α2,6-sialylation of IgG is essential for the beneficial effect of IVIg in experimental autoimmune encephalomyelitis (EAE), a Th17-driven condition, and for the reciprocal modulation of helper T-cell subsets. We observed no difference in the ability of IVIg to ameliorate EAE irrespective of its sialylation. Our findings thus show that sialylation of IVIg is not necessary for IVIg-mediated amelioration of EAE or for downregulation of Th17 cells and upregulation of regulatory T cells.
几种机制解释了静脉注射免疫球蛋白（IVIg）在自身免疫和炎症性疾病中的有益作用。这些机制包括对细胞区室和体液区室的影响。因此，IVIg 影响树突状细胞、巨噬细胞、中性粒细胞、嗜碱性粒细胞、NK 细胞以及 B 和 T 淋巴细胞。几项研究强调，IVIg 的抗炎作用取决于 IgG Fc 部分天冬酰胺-297 上 N 连接聚糖的α2,6-唾液酸化。然而，最近的报告质疑了唾液酸化 Fc 的必要性以及 FcγRIIB 在 IVIg 介导的抗炎作用中的作用。鉴于 Th17 细胞在几种自身免疫性病理中的关键作用，以及 IVIg 在其中几种情况下的使用增加，我们使用神经氨酸酶处理的去唾液酸化 IVIg，研究了 IgG 的α2,6-唾液酸化是否对 IVIg 在实验性自身免疫性脑脊髓炎（EAE）中的有益作用至关重要，EAE 是一种 Th17 驱动的疾病，以及对辅助性 T 细胞亚群的相互调节。我们观察到，无论 IVIg 是否发生唾液酸化，IVIg 改善 EAE 的能力均无差异。因此，我们的发现表明，IVIg 的唾液酸化对于 IVIg 介导的 EAE 改善或 Th17 细胞的下调和调节性 T 细胞的上调不是必需的。
