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Lectin-based Immunoassay for Aberrant IgG Glycosylation as the Biomarker for Crohn's Disease

Shinzaki, Shinichiro MD, PhD*,†; Kuroki, Eri MSc*; Iijima, Hideki MD, PhD; Tatsunaka, Norika MSc*; Ishii, Mayuko BSc*; Fujii, Hironobu BSc*; Kamada, Yoshihiro MD, PhD*,†; Kobayashi, Taku MD, PhD; Shibukawa, Narihiro MD; Inoue, Takahiro MD; Tsujii, Masahiko MD, PhD; Takeishi, Shunsaku PhD§; Mizushima, Tsunekazu MD, PhD; Ogata, Atsushi MD, PhD; Naka, Tetsuji MD, PhD**; Plevy, Scott E. MD; Takehara, Tetsuo MD, PhD; Miyoshi, Eiji MD, PhD*

doi: 10.1097/MIB.0b013e318280eade
Original Clinical Articles

Background: Easily measured and clinically useful biomarkers for inflammatory bowel disease (IBD) are required to advance patient care. We previously reported that the agalactosyl fraction among fucosylated IgG oligosaccharides is increased in IBD, especially Crohn's disease (CD). The present study aimed to establish a simple detection system for aberrant glycosylated IgG based on lectin–oligosaccharide interactions.

Methods: Lectins with higher affinity to serum IgG from IBD patients than healthy volunteers (HV) were screened by lectin microarray. Binding of selected lectins to agalactosyl IgG was definitively confirmed using step-by-step glycosidase treatment. Using the selected lectins, a lectin-enzyme-linked immunosorbent assay system was established and its clinical utility was investigated in a total of 410 (249 Japanese and 161 American) IBD patients, disease controls, and HVs.

Results: Agaricus bisporus Agglutinin (ABA) and Griffonia simplicifolia Lectin-II (GSL-II) had higher affinity for serum agalactosyl IgG from IBD patients, especially those with CD, compared to HV. Agalactosyl IgG levels measured by a lectin-enzyme immunoassay (EIA) with ABA or GSL-II were significantly increased in CD compared with HV and disease controls. Agalactosyl IgG levels significantly correlated with disease activity, showed higher predictability of therapeutic outcomes for CD than C-reactive protein levels, and exhibited higher specificity for diagnosing IBD in combination with anti-Saccharomyces cerevisiae antibody (ASCA). Validation analysis showed that agalactosyl IgG levels were significantly increased in Japanese and American CD patients.

Conclusions: A lectin-EIA for agalactosyl IgG is a novel biomarker for IBD, especially in patients with CD.

Article first published online 19 December 2012

*Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

Center for Gastrointestinal Biology and Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA

§GP BioScience Ltd., Sapporo, Hokkaido, Japan

Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

**Laboratory for Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.

Reprints: Eiji Miyoshi, MD, PhD, Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan (e-mail: emiyoshi@sahs.med.osaka-u.ac.jp).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).

The first two authors contributed equally to this work.

Received March 23, 2012

Accepted March 26, 2012

© Crohn's & Colitis Foundation of America, Inc.
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