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Original article
Predicting inflammatory bowel disease in children with abdominal pain and diarrhoea: calgranulin-C versus calprotectin stool tests
  1. Anke Heida1,
  2. Els Van de Vijver2,
  3. Don van Ravenzwaaij3,
  4. Stephanie Van Biervliet4,
  5. Thalia Z Hummel5,
  6. Zehre Yuksel6,
  7. Gieneke Gonera-de Jong7,
  8. Renate Schulenberg8,
  9. Anneke Muller Kobold9,
  10. Patrick Ferry van Rheenen1
  11. the CACATU consortium
  1. 1 Department of Paediatric Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  2. 2 Department of Paediatric Gastroenterology, University Hospital Antwerp, Edegem, Belgium
  3. 3 Department of Psychology, University of Groningen, Groningen, The Netherlands
  4. 4 Department of Paediatric Gastroenterology, University Hospital Gent, Gent, Belgium
  5. 5 Department of Paediatrics, Medisch Spectrum Twente, Enschede, The Netherlands
  6. 6 Department of Paediatrics, Ziekenhuis Groep Twente, Almelo, The Netherlands
  7. 7 Department of Paediatrics, Wilhelmina Hospital, Assen, The Netherlands
  8. 8 Department of Paediatrics, Ommelander Ziekenhuis Groningen, Winschoten, The Netherlands
  9. 9 Department of Laboratory Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
  1. Correspondence to Dr Patrick Ferry van Rheenen, Department of Pediatric Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands; p.f.van.rheenen{at}umcg.nl

Abstract

Objective Calgranulin-C (S100A12) is a new faecal marker of inflammation that is potentially more specific for inflammatory bowel disease (IBD) than calprotectin, since it is only released by activated granulocytes. We compared calgranulin-C and calprotectin to see which of the two tests best predicted IBD in children with chronic abdominal pain and diarrhoea.

Design Delayed-type cross-sectional diagnostic study.

Setting and patients Previously undiagnosed patients aged 6–17 years, who were seen in paediatric clinics in the Netherlands and Belgium, sent in a stool sample for analysis. Patients with a high likelihood of IBD underwent upper and lower endoscopy (ie, preferred reference test), while those with a low likelihood were followed for 6 months for latent IBD to become visible (ie, alternative reference test). We used Bayesian modelling to correct for differential verification bias.

Main outcome measures Primary outcome was the specificity for IBD using predefined test thresholds (calgranulin-C: 0.75 µg/g, calprotectin: 50 µg/g). Secondary outcome was the test accuracy with thresholds based on receiver operating characteristics (ROC) analysis.

Results IBD was diagnosed in 93 of 337 patients. Calgranulin-C had significantly better specificity than calprotectin when predefined thresholds were used (97% (95% credible interval (CI) 94% to 99%) vs 71% (95% CI 63% to 79%), respectively). When ROC-based thresholds were used (calgranulin-C: 0.75 µg/g, calprotectin: 400 µg/g), both tests performed equally well (specificity: 97% (95% CI 94% to 99%) vs 98% (95% CI 95% to 100%)).

Conclusions Both calgranulin-C and calprotectin have excellent test characteristics to predict IBD and justify endoscopy.

Trial registration number NCT02197780.

  • S100A12 protein
  • S100 proteins
  • inflammatory bowel disease
  • screening

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/archdischild-2017-314081

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    Footnotes

    • Contributors PFvR conceived the study. AH, EVdV, AMK and PFvR initiated the study design. PFvR is the grant holder. AH conducted the primary statistical analysis. DvR conducted the Bayesian modelling. SVB, TZH, ZY, GG-dJ and RS contributed more than 5% of the total number of participants. AH and PFvR drafted the first version of the article. All other authors revised the article critically for important intellectual content. All authors gave final approval of the version to be submitted.

    • Funding This study was supported by a grant from CisBio Bioassay (producer of Inflamark).

    • Disclaimer Neither company had a role in the design, execution, analyses, and interpretation of the data, or in the decision to submit the results.

    • Competing interests PFvR and AH received financial support from BÜHLMANN Laboratories AG (Schönenbuch, Switzerland) for other ongoing trials.

    • Patient consent Obtained.

    • Ethics approval Medical Ethical Committee of the University Medical Center in Groningen (METc 2013/503) and Antwerp University Hospital (14/40/407).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Data sharing is available on request.

    • Collaborators CACATU consortium.

    • Author note Study protocol: Published in BMJ Open 2017;7:e015636.