title: Sialylation determines the nephritogenicity of IgG3 cryoglobulins.
abstract: Monoclonal 6-19 IgG3 anti-IgG2a rheumatoid factor derived from lupus-prone MRL-Fas(lpr) mice can induce GN and cryoglobulinemia, but the features that confer nephritogenic potential are not completely understood. Asparagine-linked oligosaccharide chains of 6-19 IgG3 mAb are poorly galactosylated and hardly sialylated, possibly contributing to the pathogenic potential of 6-19 IgG3 rheumatoid factors. Here, we used the 6-19 model of cryoglobulin-associated GN to define the relative contributions of galactosylation and sialylation, in relation to cryoglobulin activity, to the nephritogenic potential of IgG3 antibodies. We generated one highly sialylated and two distinct more galactosylated 6-19 IgG3 rheumatoid factor variants. Although the mere extent of galactosylation had no effect on either the cryogenic and nephritogenic activities of 6-19 IgG3 rheumatoid factor, terminal sialylation attenuated the nephritogenic potential of 6-19 IgG3 by limiting its cryoglobulin activity. These data suggest a protective role of IgG sialylation against the development of cryoglobulin-mediated GN, highlighting the anti-inflammatory activity of sialylated IgG antibodies.
authors.affiliation: Department of Pathology and Immunology, Centre Médical Universitaire, 1211 Geneva 4, Switzerland.
authors.forename: Masako
authors.initials: M
authors.lastname: Otani
authors.forename: Aki
authors.initials: A
authors.lastname: Kuroki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Masao
authors.initials: M
authors.lastname: Kihara
authors.forename: Junichiro
authors.initials: J
authors.lastname: Nakata
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Ito
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Furukawa
authors.forename: Yasuro
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Shozo
authors.initials: S
authors.lastname: Izui
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D003449:Cryoglobulinemia / Q000209:etiology / Q000276:immunology; D003450:Cryoglobulins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D005690:Galactose / Q000737:chemistry / Q000276:immunology; D005921:Glomerulonephritis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D012217:Rheumatoid Factor / Q000737:chemistry / Q000276:immunology; D012794:Sialic Acids / Q000737:chemistry / Q000276:immunology; D012799:Sialyltransferases / Q000235:genetics; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D003450:Cryoglobulins; D017931:DNA Primers; D005690:Galactose; D007074:Immunoglobulin G; D012217:Rheumatoid Factor; D012794:Sialic Acids; D012799:Sialyltransferases; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase