Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for Crohn's disease
Article first published online: 12 JAN 2012
Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 9, pages 1723–1734, September 2012
How to Cite
Inoue, T., Iijima, H., Tajiri, M., Shinzaki, S., Shiraishi, E., Hiyama, S., Mukai, A., Nakajima, S., Iwatani, H., Nishida, T., Mizushima, T., Yasui, T., Isaka, Y., Kanto, T., Tsujii, M., Miyoshi, E., Wada, Y. and Takehara, T. (2012), Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for Crohn's disease. Inflamm Bowel Dis, 18: 1723–1734. doi: 10.1002/ibd.22876
- Issue published online: 9 AUG 2012
- Article first published online: 12 JAN 2012
- Manuscript Accepted: 19 DEC 2011
- Manuscript Received: 12 DEC 2011
- inflammatory bowel diseases;
- Crohn's disease;
- O-linked oligosaccharide;
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.
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.
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.
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;)