title: IgA nephropathy caused by unusual polymerization of IgA1 with aberrant N-glycosylation in a patient with monoclonal immunoglobulin deposition disease.
abstract: Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis characterized by the deposition of IgA immune complexes in the glomerular region. The cause of IgAN is unknown, but multiple mechanisms have been suggested. We previously reported a rare case of mesangioproliferative glomerulonephritis in a patient with monoclonal immunoglobulin deposition disease associated with monoclonal IgA1. In this study, we performed the detailed analyses of serum IgA1 from this patient in comparison with those from patients with mIgA plasma cell disorder without renal involvement and healthy volunteers. We found unusual polymerization of IgA1 with additional N-glycosylation distinctive in this patient, which was different from known etiologies. Glycan profiling of IgA1 by the lectin microarray revealed an intense signal for Wisteria floribunda agglutinin (WFA). This signal was reduced by disrupting the native conformation of IgA1, suggesting that the distinct glycan profile was reflecting the conformational alteration of IgA1, including the glycan conformation detected as additional N-glycans on both the heavy and light chains. This unusually polymerized state of IgA1 would cause an increase of the binding avidity for lectins. WFA specifically recognized highly polymerized and glycosylated IgA1. Our results of analysis in the rare case of a patient with monoclonal immunoglobulin deposition disease suggest that the formation of unusually polymerized IgA1 is caused by divergent mechanisms including multiple structural alterations of glycans, which contributes to IgA1 deposition and mesangium proliferation.
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Narimatsu
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuno
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Biochemistry, Life Sciences and Social Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ito
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kaji
authors.affiliation: Department of Nephrology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Syuzo
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Department of Nephrology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Joichi
authors.initials: J
authors.lastname: Usui
authors.affiliation: Department of Nephrology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000276:immunology*; D054794:Glycomics; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000302:isolation & purification / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism; D008970:Molecular Weight; D010265:Paraproteinemias / Q000150:complications / Q000276:immunology*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism; D037121:Plant Lectins / Q000378:metabolism; D058105:Polymerization; D011485:Protein Binding; D034781:Receptors, N-Acetylglucosamine / Q000378:metabolism; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism
chemical_list: D007070:Immunoglobulin A; D046911:Macromolecular Substances; D037121:Plant Lectins; D034781:Receptors, N-Acetylglucosamine; C040129:wisteria lectin; D014357:Trypsin; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase