Abstract
Intravenous immunoglobulin (IVIG) is the first line treatment for Guillain–Barré syndrome and multifocal motor neuropathy, which are caused by anti-ganglioside antibody-mediated complement-dependent cytotoxicity. IVIG has many potential mechanisms of action, and sialylation of the IgG Fc portion reportedly has an anti-inflammatory effect in antibody-dependent cell-mediated cytotoxicity models. We investigated the effects of different IVIG glycoforms on the inhibition of antibody-mediated complement-dependent cytotoxicity. Deglycosylated, degalactosylated, galactosylated and sialylated IgG were prepared from IVIG following treatment with glycosidases and glycosyltransferases. Sera from patients with Guillain–Barré syndrome, Miller Fisher syndrome and multifocal motor neuropathy associated with anti-ganglioside antibodies were used. Inhibition of complement deposition subsequent to IgG or IgM autoantibody binding to ganglioside, GM1 or GQ1b was assessed on microtiter plates. Sialylated and galactosylated IVIGs more effectively inhibited C3 deposition than original IVIG or enzyme-treated IVIGs (agalactosylated and deglycosylated IVIGs). Therefore, sialylated and galactosylated IVIGs may be more effective than conventional IVIG in the treatment of complement-dependent autoimmune diseases.
Highlights
Intravenous immunoglobulin (IVIG) is a therapeutic preparation of concentrated normal human polyclonal IgG obtained from plasma of several thousands of healthy donors
Malaysia) with acute motor axonal neuropathy (AMAN) associated with anti-GM1 IgG antibodies (n = 3), Miller Fisher syndrome (MFS) associated with anti-GQ1b IgG antibodies (n = 3) and multifocal motor neuropathy (MMN) associated with anti-GM1 IgM antibodies (n = 3) were collected
In the second part of the experiment, we investigated whether IVIG (Glovenin-I) and different IVIG glycoforms can inhibit complement deposition mediated by anti-GM1 and anti-GQ1b antibodies
Summary
Intravenous immunoglobulin (IVIG) is a therapeutic preparation of concentrated normal human polyclonal IgG obtained from plasma of several thousands of healthy donors. IVIG is widely used in the treatment of autoimmune and inflammatory diseases including immune-mediated neuropathies [1]. The carbohydrate moieties of human IgG determine a variety of biologic functions in health and disease [2]. A better understanding of the biological functions of the different IgG glycoforms may suggest ways of enhancing the anti-inflammatory activity of IgG concentrates. Glycosylation at both Fab and Fc portions provides a wide heterogeneity to IgG antibodies, with the variable addition of the bisecting N-acetylglucosamine, fucose to the core, as well as galactose and sialic acid to the arms of the biantennary structure (Figure 1). Glycosylation of IgG is divided into three glycoforms; galactosylated, agalactosylated and sialylated
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