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Ectopic expression of blood type antigens in inflamed mucosa with higher incidence of FUT2 secretor status in colonic Crohn’s disease

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Abstract

Background

Host–intestinal microbial interaction plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). The surface molecules of the intestinal epithelium act as receptors for bacterial adhesion and regulate the intestinal bacteria. Some known receptors are the mucosal blood type antigens, which are regulated by the fucosyltransferase2 (FUT2) gene, and individuals who express these antigens in the gastrointestinal tract are called secretors. Recent research has revealed that the FUT2 gene is associated with Crohn’s disease (CD) in western populations.

Methods

To clarify the contribution of mucosal blood type antigens in IBD, we determined the incidence of five previously reported single-nucleotide polymorphisms of the FUT2 gene in Japanese patients. We also used immunohistochemistry to investigate the antigen expression in mucosal specimens from IBD patients and animal models.

Results

Genetic analysis revealed that all of the patients with colonic CD were secretors, whereas the incidence of secretors was 80, 80, 67, and 80%, respectively, for the control, ileocolonic CD, ileal CD, and ulcerative colitis groups (P = 0.036). Abnormal expression of blood type antigens was observed only in colonic CD. Interleukin-10−/− mice, but not dextran sulfate sodium colitis mice, had enhanced colonic expression of blood type antigens, and the expression of these antigens preceded the development of colitis in the interleukin-10−/− mice.

Conclusions

FUT2 secretor status was associated with colonic-type CD. This finding, taken together with the immunohistochemistry data, suggests that the abnormal expression of blood type antigens in the colon may be a unique and essential factor for colonic CD.

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Acknowledgments

This work was supported in part by a Keio University Grant-in-Aid for Encouragement of Young Medical Scientists, and KORP project from Otsuka Pharmaceutical Co., Ltd.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Jun Miyoshi, Tomoharu Yajima, Susumu Okamoto, Katsuyoshi Matsuoka, Tadakazu Hisamatsu, Katsuyoshi Shimamura, Atsushi Nakazawa, Takanori Kanai & Toshifumi Hibi

  2. Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, Tokyo, Japan

    Nagamu Inoue, Haruhiko Ogata & Yasushi Iwao

  3. Division of Diagnostic Pathology, School of Medicine, Keio University, Tokyo, Japan

    Makio Mukai

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  1. Jun Miyoshi
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Correspondence to Toshifumi Hibi.

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Miyoshi, J., Yajima, T., Okamoto, S. et al. Ectopic expression of blood type antigens in inflamed mucosa with higher incidence of FUT2 secretor status in colonic Crohn’s disease. J Gastroenterol 46, 1056–1063 (2011). https://doi.org/10.1007/s00535-011-0425-7

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  • DOI: https://doi.org/10.1007/s00535-011-0425-7

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