title: IgA1 molecules produced by tonsillar lymphocytes are under-O-glycosylated in IgA nephropathy.
abstract: BACKGROUND
  Human serum immunoglobulin A1 (IgA1) has a unique mucine-like structure in its hinge region that contains O-glycans and proline-rich peptides. We previously reported the under-O-glycosylation of the hinge in serum IgA1 and deposited IgA1 in glomeruli (glomerular IgA1) in IgA nephropathy. The clinical development and exacerbation of IgA nephropathy frequently are preceded by episodes of upper respiratory tract infections. Therefore, tonsils, which represent the predominant immunocompetent tissue of the upper respiratory tract, may be related to the pathogenesis of IgA nephropathy. In this study, we investigated the O-glycan structure of IgA1 produced by tonsillar lymphocytes (tonsillar IgA1), suspecting that tonsillar IgA1 is one of the origins of glomerular IgA1 in patients with IgA nephropathy.
  
  
  METHODS
  Extracted tonsils were obtained from 7 patients with IgA nephropathy and 5 patients with chronic tonsillitis as controls. Tonsillar lymphocytes separated from extracted tonsils were cultured for 7 days, and IgA1 in the culture medium was purified. The varieties of O-glycans in tonsillar IgA1 were determined from the molecular weights measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
  
  
  RESULTS
  A significant increase in the percentage of asialo-agalacto type O-glycans was found in tonsillar IgA1 in 4 of 7 patients with IgA nephropathy (57.1%) compared with controls. Between the IgA nephropathy and control groups, the difference was statistically significant (P = 0.047).
  
  
  CONCLUSIONS
  This study provides precise information about the structure of O-glycans in tonsillar IgA1 in patients with IgA nephropathy. Our results suggest that tonsils produced the underglycosylated IgA1 molecules in patients with IgA nephropathy.
authors.affiliation: Department of In-Home Medicine, Nagoya University School of Medicine, Nagoya, Aichi, Japan. akeyo-n@kb3.so-net.ne.jp
authors.forename: Akeyo
authors.initials: A
authors.lastname: Horie
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hiki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Odani
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Mami
authors.initials: M
authors.lastname: Takahashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Hitoo
authors.initials: H
authors.lastname: Iwase
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Izumi
authors.initials: I
authors.lastname: Nakashima
authors.forename: Kenji
authors.initials: K
authors.lastname: Maeda
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000276:immunology* / Q000473:pathology; D011134:Polysaccharides / Q000032:analysis; D011499:Protein Processing, Post-Translational; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014068:Tonsillectomy
chemical_list: D007070:Immunoglobulin A; D011134:Polysaccharides