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Increased suppressor of cytokine signaling-3 expression predicts mucosal relapse in ulcerative colitis

Authors

  • Yi Li MD, PhD,

    Corresponding author
    1. Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands
    2. Department of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine, Renji Hospital, Shanghai, China
    • Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, No. 1630 Dong Fang Road, Shanghai, 200127, P.R. China
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  • Veerle J.A.A. Nuij MD,

    1. Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands
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  • Judith E. Baars MD, PhD,

    1. Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands
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  • Katharina Biermann MD, PhD,

    1. Department of Pathology, Erasmus Medical Center, Rotterdam, Netherlands
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  • Ernst J. Kuipers MD, PhD,

    1. Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands
    2. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands
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  • Maikel P. Peppelenbosch MD, PhD,

    1. Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands
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  • Colin de Haar MD, PhD,

    1. Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands
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    • The last two authors share senior authorship.

  • C. Janneke van der Woude MD, PhD

    1. Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands
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    • The last two authors share senior authorship.


Abstract

Background:

Most biomarkers predicting mucosal relapse of ulcerative colitis (UC) patients in clinical remission represent low levels of mucosal inflammation. Since SOCS3 expression may increase the vulnerability of intestinal epithelial cells (IECs) to various insults, we investigated whether its expression predicts mucosal relapse in UC patients in clinical remission without any signs of mucosal inflammation.

Methods:

UC patients (n = 32) in clinical, endoscopic, and histological remission were followed up for 9 years. IEC expression of SOCS3, p-STAT3, and p-STAT1 were assessed with biopsies from the baseline colonoscopy, last colonoscopy before relapse, and colonoscopy at relapse. Clinical data, endoscopy, and histology reports were collected from patient charts.

Results:

Twenty-six (81%) patients had histological relapse, 19 (59%) developed an endoscopic relapse, and 17 (53%) had a clinical relapse during follow-up. SOCS3 expression at first colonoscopy during remission correlated with shorter time to histological, endoscopic, and clinical relapse. SOCS3 expression was increased at the last colonoscopy before relapse, approaching relapse levels, whereas p-STAT3 expression was low during the entire remission. A positive correlation between IEC SOCS3 and its inducer p-STAT1 was shown.

Conclusions:

SOCS3 IEC expression during remission may be useful in predicting mucosal relapse in patients without any signs of mucosal inflammation. These data strengthen our hypothesis that SOCS3 contributes to enhanced vulnerability of IEC during remission. Thus, SOCS3 levels during remission may function as a therapeutic target for clinical monitoring and early induction of mucosal healing. (Inflamm Bowel Dis 2012;)

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