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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Volume 56, Issue 1


Reference values of fecal calgranulin C (S100A12) in school aged children and adolescents

Anke HeidaORCID iD: http://orcid.org/0000-0001-5429-1884 / Anneke C. Muller Kobold
  • Department of Laboratory Medicine, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lucie Wagenmakers
  • Department of Laboratory Medicine, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Koos van de Belt
  • Department of Laboratory Medicine, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Patrick F. van Rheenen
  • Corresponding author
  • Department of Pediatric Gastroenterology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-07-14 | DOI: https://doi.org/10.1515/cclm-2017-0152



Calgranulin C (S100A12) is an emerging marker of inflammation. It is exclusively released by activated neutrophils which makes this marker potentially more specific for inflammatory bowel disease (IBD) compared to established stool markers including calprotectin and lactoferrin. We aimed to establish a reference value for S100A12 in healthy children and investigated whether S100A12 levels can discriminate children with IBD from healthy controls.


In a prospective community-based reference interval study we collected 122 stool samples from healthy children aged 5–19 years. Additionally, feces samples of 41 children with suspected IBD (who were later confirmed by endoscopy to have IBD) were collected. Levels of S100A12 were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) (Inflamark®). The limit of detection was 0.22 μg/g.


The upper reference limit in healthy children was 0.75 μg/g (90% confidence interval: 0.30–1.40). Median S100A12 levels were significantly higher in patients with IBD (8.00 μg/g [interquartile range (IQR) 2.5–11.6] compared to healthy controls [0.22 μg/g (IQR<0.22); p<0.001]). The best cutoff point based on receiver operating characteristic curve was 0.33 μg/g (sensitivity 93%; specificity 97%).


Children and teenagers with newly diagnosed IBD have significantly higher S100A12 results compared to healthy individuals. We demonstrate that fecal S100A12 shows diagnostic promise under ideal testing conditions. Future studies need to address whether S100A12 can discriminate children with IBD from non-organic disease in a prospective cohort with chronic gastrointestinal complaints, and how S100A12 performs in comparison with established stool markers.

This article offers supplementary material which is provided at the end of the article.

Keywords: adolescent; child; inflammatory bowel disease; reference value; S100A12 protein; S100 proteins

Article note:

An interim analysis of this study was orally presented at the ESPGHAN Annual Meeting in Athens in 2016.


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About the article

Corresponding author: Patrick F. van Rheenen, MD, PhD, Department of Pediatric Gastroenterology, University Medical Center Groningen, University of Groningen, Internal Code CA 31, PO Box 30001, 9700 RB Groningen, The Netherlands, Phone: +31 30 3614147

Received: 2017-02-22

Accepted: 2017-04-25

Published Online: 2017-07-14

Published in Print: 2017-11-27

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: This study was supported by CisBio Bioassay, Codolet, France (developer and producer of Inflamark®). Trial registry: Clinical trials.gov NCT02588222.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 1, Pages 126–131, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0152.

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