title: Lack of galactosylation enhances the pathogenic activity of IgG1 but Not IgG2a anti-erythrocyte autoantibodies.
abstract: IgG bears asparagine-linked oligosaccharide side chains in the Fc region. Variations in their extent of galactosylation and sialylation could modulate IgG Fc-dependent effector functions, and hence Ab activity. However, it has not yet been clarified whether the pathogenic potential of IgG autoantibodies is consistently enhanced by the absence of galactose residues per se or the lack of terminal sialylation, which is dependent on galactosylation. Moreover, it remains to be defined whether the increased pathogenicity of agalactosylated IgG is related to activation of the complement pathway by mannose-binding lectin, as suggested by in vitro studies. Using a murine model of autoimmune hemolytic anemia, we defined the contribution of galactosylation or sialylation to the pathogenic activity of IgG1 and IgG2a anti-erythrocyte class-switch variants of 34-3C monoclonal autoantibody. We generated their degalactosylated or highly sialylated glycovariants and compared their pathogenic effects with those of highly galactosylated or desialylated counterparts. Our results demonstrated that lack of galactosylation, but not sialylation, enhanced the pathogenic activity of 34-3C IgG1, but not IgG2a autoantibodies. Moreover, analysis of in vivo complement activation and of the pathogenic activity in mice deficient in C3 or IgG FcRs excluded the implication of mannose-binding lectin-mediated complement activation in the enhanced pathogenic effect of agalactosylated IgG1 anti-erythrocyte autoantibodies.
authors: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland;
authors: Kiyoaki
authors: K
authors: Ito
authors: Jun-ichi
authors: J
authors: Furukawa
authors: Kazunori
authors: K
authors: Yamada
authors: Ngoc Lan
authors: NL
authors: Tran
authors: Yasuro
authors: Y
authors: Shinohara
authors: Shozo
authors: S
authors: Izui
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011961:Receptors, Fc / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D011961:Receptors, Fc; C064155:agalactosyl IGG