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.

journal_name

Inflamm Bowel Dis

authors

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,Takehara T

doi

10.1002/ibd.22876

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

1723-34

issue

9

eissn

1078-0998

issn

1536-4844

journal_volume

18

pub_type

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