title: Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for Crohn's disease.
abstract: BACKGROUND
  Ideal biomarkers are required to be developed for the diagnosis and prediction of the treatment of inflammatory bowel disease (IBD). We have reported that alteration of N-linked oligosaccharides of immunoglobulin (Ig) G is a novel diagnostic marker of IBD. Oligosaccharide alterations of IgA, however, have not been investigated in IBD patients.
  
  
  METHODS
  N- and O-linked oligosaccharides of serum IgA purified from 32 patients with Crohn's disease (CD), 30 patients with ulcerative colitis (UC), and 30 healthy volunteers (HV) were analyzed with high-performance liquid chromatography and mass spectrometry. Enzymes related to oligosaccharide attachment were investigated.
  
  
  RESULTS
  N-linked oligosaccharides of IgA were not different between IBD and HV. In contrast, the number of N-acetylgalactosamines per hinge glycopeptide (GalNAc/HP) in the O-linked oligosaccharides of IgA was significantly decreased in patients with CD compared with UC and HV. GalNAc/HP had high sensitivity and specificity for discriminating between CD and HV based on receiver operating characteristic analysis. Lower GalNAc/HP was associated with more severe disease activity of CD. Changes in GalNAc/HP levels in 6 weeks after treatment with infliximab were associated with the clinical activity of CD at 30 weeks. GalNAc transferase expression of naïve B cells and extent of GalNAc attachment in IgA were significantly decreased by interleukin-21 in vitro.
  
  
  CONCLUSIONS
  The number of GalNAc attached in the IgA O-linked glycans of CD patients was significantly decreased, and strongly correlated with the clinical activity. Alterations of GalNAc attachment in IgA could be useful as a novel diagnostic and prognostic marker of CD.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inoue
authors.forename: Hideki
authors.initials: H
authors.lastname: Iijima
authors.forename: Michiko
authors.initials: M
authors.lastname: Tajiri
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Shinzaki
authors.forename: Eri
authors.initials: E
authors.lastname: Shiraishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hiyama
authors.forename: Akira
authors.initials: A
authors.lastname: Mukai
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nakajima
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Iwatani
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nishida
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.forename: Teruhito
authors.initials: T
authors.lastname: Yasui
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsujii
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Wada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
mesh_terms: D000116:Acetylgalactosamine / Q000172:deficiency*; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015153:Blotting, Western; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003093:Colitis, Ulcerative / Q000097:blood / Q000175:diagnosis*; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007070:Immunoglobulin A / Q000097:blood*; D037102:Lectins / Q000378:metabolism; D008297:Male; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D009844:Oligosaccharides / Q000097:blood*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D000116:Acetylgalactosamine; D015415:Biomarkers; D007070:Immunoglobulin A; D037102:Lectins; D017350:N-Acetylgalactosaminyltransferases; D009844:Oligosaccharides; D012333:RNA, Messenger; D000097763:Polypeptide N-acetylgalactosaminyltransferase