Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for Crohn's disease

Authors

  • Takahiro Inoue MD,

    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Hideki Iijima MD, PhD,

    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Michiko Tajiri BS,

    1. Research Institute, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan
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  • Shinichiro Shinzaki MD, PhD,

    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Eri Shiraishi MD,

    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Satoshi Hiyama MD,

    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Akira Mukai MD,

    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Sachiko Nakajima MD, PhD,

    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Hirotsugu Iwatani MD, PhD,

    1. Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Tsutomu Nishida MD, PhD,

    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Tsunekazu Mizushima MD, PhD,

    1. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Teruhito Yasui PhD,

    1. Department of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan
    2. Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
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  • Yoshitaka Isaka MD, PhD,

    1. Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Tatsuya Kanto MD, PhD,

    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    2. Department of Dendritic Cell Biology and Clinical Application, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Masahiko Tsujii MD, PhD,

    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Eiji Miyoshi MD, PhD,

    1. Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Yoshinao Wada MD, PhD,

    1. Research Institute, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan
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  • Tetsuo Takehara MD, PhD

    Corresponding author
    1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    • Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka 565-0871, Japan
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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. (Inflamm Bowel Dis 2012;)

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