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Clinical Chemistry and Laboratory Medicine (CCLM)

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

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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1437-4331
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Volume 56, Issue 1

Issues

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

Abstract

Background:

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.

Methods:

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.

Results:

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%).

Conclusions:

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.

References

  • 1.

    van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. Br Med J 2010;341:c3369.CrossrefWeb of ScienceGoogle Scholar

  • 2.

    Degraeuwe PL, Beld MP, Ashorn M, Canani RB, Day AS, Diamanti A, et al. Faecal calprotectin in suspected paediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2015;60: 339–46.Web of ScienceCrossrefPubMedGoogle Scholar

  • 3.

    Van de Vijver E, Schreuder AB, Cnossen WR, Muller Kobold AC, van Rheenen PF. Safely ruling out inflammatory bowel disease in children and teenagers without referral for endoscopy. Arch Dis Child 2012;97:1014–8.Web of ScienceCrossrefPubMedGoogle Scholar

  • 4.

    Heida A, Holtman GA, Lisman-Van Leeuwen Y, Berger MY, Van Rheenen PF. Avoid endoscopy in children with suspected inflammatory bowel disease who have normal calprotectin levels. J Pediatr Gastroenterol Nutr 2016;62:47–9.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 5.

    Däbritz J, Musci J, Foell D. Diagnostic utility of faecal biomarkers in patients with irritable bowel syndrome. World J Gastroenterol 2014;20:363–75.CrossrefWeb of SciencePubMedGoogle Scholar

  • 6.

    Foell D, Wittkowski H, Roth J. Monitoring disease activity by stool analyses: from occult blood to molecular markers of intestinal inflammation and damage. Gut 2009;58:859–68.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 7.

    Sidler MA, Leach ST, Day AS. Fecal S100A12 and fecal calprotectin as noninvasive markers for inflammatory bowel disease in children. Inflamm Bowel Dis 2008;14:359–66.Web of ScienceCrossrefPubMedGoogle Scholar

  • 8.

    Foell D, Wittkowski H, Ren Z, Turton J, Pang G, Daebritz J, et al. Phagocyte-specific S100 proteins are released from affected mucosa and promote immune responses during inflammatory bowel disease. J Pathol 2008:183–92.PubMedWeb of ScienceGoogle Scholar

  • 9.

    Lasson A, Stotzer P-O, Ohman L, Isaksson S, Sapnara M, Strid H. The intra-individual variability of faecal calprotectin: a prospective study in patients with active ulcerative colitis. J Crohn’s Colitis 2015;9:26–32.Google Scholar

  • 10.

    de Jong NS, Leach ST, Day AS. Fecal S100A12: a novel noninvasive marker in children with Crohn’s disease. Inflamm Bowel Dis 2006;12:566–72.PubMedCrossrefGoogle Scholar

  • 11.

    Olafsdottir E, Aksnes L, Fluge G, Berstad A. Faecal calprotectin levels in infants with infantile colic, healthy infants, children with inflammatory bowel disease, children with recurrent abdominal pain and healthy children. Acta Paediatr 2002;91:45–50.CrossrefPubMedGoogle Scholar

  • 12.

    Hestvik E, Tumwine JK, Tylleskar T, Grahnquist L, Ndeezi G, Kaddu-Mulindwa DH, et al. Faecal calprotectin concentrations in apparently healthy children aged 0–12 years in urban Kampala, Uganda: a community-based survey. BMC Pediatr 2011;11:9.CrossrefWeb of SciencePubMedGoogle Scholar

  • 13.

    Oord T, Hornung N. Fecal calprotectin in healthy children. Scand J Clin Lab Invest 2014;74:254–8.Web of ScienceCrossrefPubMedGoogle Scholar

  • 14.

    Zhu Q, Li F, Wang J, Shen L, Sheng X. Fecal calprotectin in healthy children aged 1–4 years. PLoS One 2016;11:e0150725.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 15.

    Fagerberg UL, Lööf L, Merzoug RD, Hansson L-O, Finkel Y. Fecal calprotectin levels in healthy children studied with an improved assay. J Pediatr Gastroenterol Nutr 2003;37:468–72.CrossrefPubMedGoogle Scholar

  • 16.

    Rugtveit J, Fagerhol MK. Age-dependent variations in fecal calprotectin concentrations in children. J Pediatr Gastroenterol Nutr 2002;34:323–4, 324–5.CrossrefGoogle Scholar

  • 17.

    Day AS, Ehn M, Gearry RB, Lemberg DA, Leach ST. Fecal S100A12 in healthy infants and children. Dis Markers 2013;35:295–9.Web of ScienceCrossrefPubMedGoogle Scholar

  • 18.

    Levine A, Koletzko S, Turner D, Escher JC, Cucchiara S, de Ridder L, et al. ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr 2014;58:795–806.Web of ScienceGoogle Scholar

  • 19.

    CLSI. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline, 3rd ed. CLSI document C28-A3c. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.Google Scholar

  • 20.

    Dixon W. Processing data for ourliers. Biometrics 1953;9:74–89.CrossrefGoogle Scholar

  • 21.

    Reed AH, Henry RJ, Mason WB. Influence of statistical method used on the resulting estimate of normal range. Clin Chem 1971;17:275–84.PubMedGoogle Scholar

  • 22.

    Nylund CM, D’Mello S, Kim M-O, Bonkowski E, Däbritz J, Foell D, et al. Granulocyte macrophage-colony-stimulating factor autoantibodies and increased intestinal permeability in Crohn disease. J Pediatr Gastroenterol Nutr 2011;52:542–8.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 23.

    Foell D, Kucharzik T, Kraft M, Vogl T, Sorg C, Domschke W, et al. Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease. Gut 2003;52:847–53.CrossrefPubMedGoogle Scholar

  • 24.

    Yang Z, Tao T, Raftery MJ, Youssef P, Di Girolamo N, Geczy CL. Proinflammatory properties of the human S100 protein S100A12. J Leukoc Biol 2001;69:986–94.PubMedGoogle Scholar

  • 25.

    Kaiser T, Langhorst J, Wittkowski H, Becker K, Friedrich AW, Rueffer A, et al. Faecal S100A12 as a non-invasive marker distinguishing inflammatory bowel disease from irritable bowel syndrome. Gut 2007;56:1706–13.Web of ScienceCrossrefPubMedGoogle Scholar

  • 26.

    Fournier BM, Parkos CA. The role of neutrophils during intestinal inflammation. Mucosal Immunol 2012;5:354–66.Web of SciencePubMedCrossrefGoogle Scholar

  • 27.

    Sackett DL, Haynes RB. The architecture of diagnostic research. Br Med J 2002;324:539–41.CrossrefGoogle Scholar

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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