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

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 naive 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;)