title: O-glycosylation of serum IgD in IgA nephropathy.
abstract: In IgA nephropathy (IgAN), serum IgA1 with abnormal O-glycosylation preferentially deposits in the glomerular mesangium. The control of O-glycosylation is poorly understood. Among Ig isotypes, only IgD, produced early in B cell development, and IgA1, produced by mature B cells, are O-glycosylated. For investigation of the stage of B cell maturation at which the defect seen in IgAN arises, the O-glycosylation of serum IgA1 and IgD was studied in IgAN and controls. Serum was obtained from 20 patients with IgAN and 20 control subjects. The O-glycosylation profiles of native and desialylated IgA1 and IgD were measured in an ELISA-type system using the lectins Helix aspersa and peanut agglutinin, which bind to alternative forms of O-glycan moieties. The lectin-binding patterns of the two immunoglobulins differed in all participants, with that of IgD suggesting that it is more heavily galactosylated than IgA1. Defective O-glycosylation of IgA1, probably taking the form of reduced galactosylation, was confirmed in IgAN in this study. This undergalactosylation was not shared by IgD; in contrast, IgD carried more galactosylated O-glycans in IgAN than controls. The contrasting lectin-binding patterns of IgA1 and IgD shows that Ig O-glycosylation is differentially controlled during B cell maturation. Compared with controls, O-glycosylation in IgAN is incomplete in IgA1 but more complete in IgD. These observations show that abnormal IgA1 O-glycosylation in IgAN is not due to an inherent defect in glycosylation mechanisms but arises only at a later stage in B cell development and may be secondary to aberrant immunoregulation.
authors.affiliation: John Walls Renal Unit, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. aa50@le.ac.uk
authors.forename: Alice C
authors.initials: AC
authors.lastname: Smith
authors.forename: Jacob F
authors.initials: JF
authors.lastname: de Wolff
authors.forename: Karen
authors.initials: K
authors.lastname: Molyneux
authors.forename: John
authors.initials: J
authors.lastname: Feehally
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barratt
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001665:Binding Sites; D002240:Carbohydrate Sequence; D016022:Case-Control Studies; D002454:Cell Differentiation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005690:Galactose / Q000737:chemistry; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000737:chemistry; D007072:Immunoglobulin D / Q000097:blood* / Q000737:chemistry; D037102:Lectins; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
chemical_list: D007070:Immunoglobulin A; D007072:Immunoglobulin D; D037102:Lectins; D005690:Galactose