title: Identification of distinct glycoforms of IgA1 in plasma from patients with immunoglobulin A (IgA) nephropathy and healthy individuals.
abstract: Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis worldwide and is histologically characterized by the deposition of IgA1 and consequent inflammation in the glomerular mesangium. Prior studies suggested that serum IgA1 from IgAN patients contains aberrant, undergalactosylated O-glycans, for example, Tn antigen and its sialylated version, SialylTn (STn), but the mechanisms underlying aberrant O-glycosylation are not well understood. Here we have used serial lectin separation technologies, Western blot, enzymatic modifications, and mass spectrometry to explore whether there are different glycoforms of IgA1 in plasma from patients with IgAN and healthy individuals. Although total plasma IgA in IgAN patients was elevated ∼ 1.6-fold compared with that in healthy donors, IgA1 in all samples was unexpectedly separable into two distinct glycoforms: one with core 1 based O-glycans, and the other exclusively containing Tn/STn structures. Importantly, Tn antigen present on IgA1 from IgAN patients and controls was convertible into the core 1 structure in vitro by recombinant T-synthase. Our results demonstrate that undergalactosylation of O-glycans in IgA1 is not restricted to IgAN and suggest that in vivo inefficiency of T-synthase toward IgA1 in a subpopulation of B or plasma cells, as well as overall elevation of IgA, may contribute to IgAN pathogenesis.
authors: From the Departments of ‡Biochemistry and.
authors: Sylvain
authors: S
authors: Lehoux
authors: From the Departments of ‡Biochemistry and.
authors: Rongjuan
authors: R
authors: Mi
authors: From the Departments of ‡Biochemistry and.
authors: Rajindra P
authors: RP
authors: Aryal
authors: From the Departments of ‡Biochemistry and.
authors: Yingchun
authors: Y
authors: Wang
authors: §Department of Cellular and Molecular Medicine, Copenhagen Center for Glycomics, Copenhagen, Denmark;
authors: Katrine T-B G
authors: KT
authors: Schjoldager
authors: §Department of Cellular and Molecular Medicine, Copenhagen Center for Glycomics, Copenhagen, Denmark;
authors: Henrik
authors: H
authors: Clausen
authors: ¶Department of Molecular Cell Biology & Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Irma
authors: I
authors: van Die
authors: ‖Medicine, Emory University School of Medicine, Atlanta, GA 30322;
authors: Yoosun
authors: Y
authors: Han
authors: ‖Medicine, Emory University School of Medicine, Atlanta, GA 30322;
authors: Arlene B
authors: AB
authors: Chapman
authors: From the Departments of ‡Biochemistry and.
authors: Richard D
authors: RD
authors: Cummings
authors: From the Departments of ‡Biochemistry and tju@emory.edu.
authors: Tongzhong
authors: T
authors: Ju
mesh_terms: D000328:Adult; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D005690:Galactose / Q000378:metabolism; D005700:Galactosyltransferases / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000097:blood*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000145:classification / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D037102:Lectins / Q000276:immunology; D008297:Male; D019887:Peanut Agglutinin / Q000276:immunology; D011134:Polysaccharides / Q000097:blood / Q000378:metabolism*; D012799:Sialyltransferases / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; C038095:Helix lectin; D007070:Immunoglobulin A; D037102:Lectins; D019887:Peanut Agglutinin; D011134:Polysaccharides; C040286:Tn antigen; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases; D012799:Sialyltransferases; C088391:galactosyl-1-3-N-acetylgalactosaminyl-specific 2,6-sialyltransferase; D005690:Galactose