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O-linked Oligosaccharide Alterations of IgA1 are a Novel Biological Marker of Patients with Inflammatory Bowel Disease

Digestive diseases and sciences, 2022-05, Vol.56 (10), p.2772 [Peer Reviewed Journal]

COPYRIGHT 2022 Springer ;ISSN: 0163-2116 ;EISSN: 1573-2568

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  • Title:
    O-linked Oligosaccharide Alterations of IgA1 are a Novel Biological Marker of Patients with Inflammatory Bowel Disease
  • Author: Inoue, Takahiro ; Iijima, Co-authors Hideki ; Nakajima, Sachiko ; Shinzaki, Shinichiro ; Nishida, Tsutomu ; Kanto, Tatsuya ; Tsujii, Masahiko ; Wada, Yoshinao ; Miyoshi, Eiji ; Takehara, Tetsuo
  • Subjects: Analysis ; Appendicitis ; Diagnosis ; Galactose ; Immunoglobulin A ; Immunoglobulin G ; Mass spectrometry ; Medical research ; Medicine, Experimental ; Ulcerative colitis
  • Is Part Of: Digestive diseases and sciences, 2022-05, Vol.56 (10), p.2772
  • Description: Introduction: The authors have recently shown that terminal galactose is significantly depleted in the N-linked oligosaccharides of serum immunoglobulin G (IgG) in inflammatory bowel diseases (IBD), and that the alterations can be a novel diagnostic marker. However, oligosaccharide alterations of IgA1 have not been investigated in IBD. The purpose of this study was to evaluate the oligosaccharide alterations of IgA1 glycans in IBD patients. Methods: Serum samples were collected from 32 patients with Crohn's disease (CD), 30 patients with ulcerative colitis (UC), 30 healthy volunteers (HV), 17 patients with colonic inflammation including appendicitis, diverticulitis, and ischemic colitis (disease control; DC), and 10 patients with IgA nephropathy (IgAN). N-linked oligosaccharides of IgA1 were analyzed by HPLC, and O-Linked oligosaccharides with IgA1 hinge peptides were analyzed by mass spectrometry. Result: The HPLC profiles of the N-linked oligosaccharides have shown that galactose deficient of IgG N-glycans did not extend to IgA1. In contrast, the mass spectra have shown that the number of attached GalNAc per each hinge peptides (GalNAc/HP) was significantly decreased in patients with CD and IgAN compared to patients with UC, DC and HV (p < 0.01). In addition, GalNAc/HP was significantly decreased in UC compared to HV (p < 0.05). Furthermore, the GalNAc/HP was significantly lower in CDAI > 150 and Montreal category B2 + B3, indicating that the decrease of GalNAc in IgA1 O-linked oligosaccharides was associated with worsening of the disease status of IBD. When the attached GalNAc was used as a serologic marker to discriminate between HV and CD, the AUC in ROC analysis of GalNAc/HP was superior to that of ASCA. Conclusion: The number of GalNAc attached to the IgA1 O-linked glycopeptides of IBD patients was significantly decreased, and was remarkably correlated to the clinical findings. The data suggest that GalNAc attachment to the IgA1 can be a novel diagnostic marker of IBD.
  • Publisher: Springer
  • Language: English
  • Identifier: ISSN: 0163-2116
    EISSN: 1573-2568
  • Source: ProQuest Central
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