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Improving Relapse Prediction in Inflammatory Bowel Disease by Neutrophil-Derived S100A12

Däbritz, Jan MD*,†,‡; Langhorst, Jost MD§; Lügering, Andreas MD; Heidemann, Jan MD; Mohr, Miriam MD§; Wittkowski, Helmut MD*; Krummenerl, Thomas MD**; Foell, Dirk MD*,†

doi: 10.1097/MIB.0b013e318280b1cd
Original Clinical Article

Background: Prediction of inflammatory bowel disease relapse has important implications for therapeutic strategies. Fecal S100A12 has been reported as a novel marker of intestinal inflammation. The objective was to investigate the utility of S100A12 as a marker for the confirmation of stable remission and prediction of relapses.

Methods: We consecutively included 147 adults and 34 children with Crohn’s disease (n = 61) or ulcerative colitis (n = 120). Over a 3-year period, we collected 686 stool samples and 861 serum samples during regular follow-up visits. S100A12 and calprotectin levels were measured by an enzyme-linked immunoassay.

Results: Fecal S100A12 correlated with S100A12 serum levels, other laboratory markers, as well as disease activity, location, and behavior. Fecal S100A12 levels in the relapse group differed significantly from those of the nonrelapse group. A baseline fecal S100A12 level of >0.5 mg/kg was significantly associated with disease relapse within 18 months. Time course analysis of fecal S100A12 before and after relapse showed a clear increase of S100A12 concentrations up to 6 months before clinical relapse. At 0.43 mg/kg, the sensitivity and specificity of S100A12 for predicting relapse already 8 to 12 weeks earlier were 70% and 83%, respectively.

Conclusions: Regular measurements of fecal S100A12 levels reliably detect inflammatory bowel disease relapse at an early stage, which makes the test a promising noninvasive tool for monitoring and optimizing therapy, and may reduce the need for invasive investigations during disease follow-up.

Article first published online 31 December 2012

*Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster, Germany

Interdisciplinary Center of Clinical Research, University of Münster, Münster, Germany

The Royal Children's Hospital Melbourne, Murdoch Childrens Research Institute, Parkville, Australia

§Department of Integrative Gastroenterology, Internal and Integrative Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen, Duisburg-Essen, Germany

MVZ Portal 10, Münster, Germany

Department of Gastroenterology, Klinikum Bielefeld Mitte, Bielefeld, Germany

**Gastroenterology Clinic, Germania Campus Münster, Münster, Germany.

Reprints: Jan Däbritz, MD, University Hospital Münster, Department of Pediatric Rheumatology and Immunology, Röntgenstr. 21, D-48149 Münster, Germany (e-mail:

Supported by a grant of the Crohn’s and Colitis Foundation of America (D.F. and J.D.). The sponsor had no involvement in the study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the manuscript for publication.

J. Däbritz and J. Langhorst contributed equally and are both first authors.

The authors have no conflicts of interest to disclose.

Received July 17, 2012

Accepted August 20, 2012

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