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Improving IBD diagnosis and monitoring by understanding preanalytical, analytical and biological fecal calprotectin variability

  • Andrea Padoan ORCID logo , Renata D’Incà , Maria Luisa Scapellato , Rudi De Bastiani , Roberta Caccaro , Claudia Mescoli , Stefania Moz , Dania Bozzato , Carlo-Federico Zambon , Greta Lorenzon , Massimo Rugge , Mario Plebani ORCID logo and Daniela Basso EMAIL logo
Published/Copyright: May 5, 2018
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 56 Issue 11

Abstract

Background:

The appropriate clinical use of fecal calprotectin (fCal) might be compromised by incomplete harmonization between assays and within- and between-subjects variability. Our aim was to investigate the analytical and biological variability of fCal in order to provide tools for interpreting fCal in the clinical setting.

Methods:

Experiments were conducted to investigate the effects of temperature and storage time on fCal. Thirty-nine controls were enrolled to verify biological variability, and a case-control study was conducted on 134 controls and 110 IBD patients to compare the clinical effectiveness of three different fCal assays: ELISA, CLIA and turbidimetry.

Results:

A 12% decline in fCal levels was observed within 24 h following stool collection irrespective of storage temperature. Samples were unstable following a longer storage time interval at room temperature. Within- and between-subjects fCal biological variability, at 31% and 72% respectively, resulted in a reference change value (RCV) in the region of 100%. fCal sensitivity in distinguishing between controls and IBD patients is satisfactory (68%), and the specificity high (93%) among young (<65 years), but not among older (≥65 years) subjects (ROC area: 0.584; 95% CI: 0.399–0.769). Among the young, assays have different optimal thresholds (120 μg/g for ELISA, 50 μg/g for CLIA and 100 μg/g for turbidimetry).

Conclusions:

We recommend a standardized preanalytical protocol for fCal, avoiding storage at room temperature for more than 24 h. Different cutoffs are recommended for different fCal assays. In monitoring, the difference between two consecutive measurements appears clinically significant when higher than 100%, the fCal biological variability-derived RCV.

Keywords: biological variability; calprotectin; Crohn’s disease; inflammatory bowel diseases; ulcerative colitis
Corresponding author: Daniela Basso, MD, Department of Medicine – DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy, Phone: +390498212801, Fax: +390498211981

Acknowledgments

The authors thank Mrs. Monica Razetti and Cinzia Centobene for their valuable technical help in performing the analyses.

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

  2. Research funding: University of Padova, Department of Medicine – DIMED: BIRD173078/17.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.

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Supplementary Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2018-0134).

Received: 2018-02-05
Accepted: 2018-04-03
Published Online: 2018-05-05
Published in Print: 2018-10-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2018-0134
Keywords for this article
biological variability; calprotectin; Crohn’s disease; inflammatory bowel diseases; ulcerative colitis

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. New biomarkers and traditional cardiovascular risk scores: any crystal ball for current effective advice and future exact prediction?
  4. Reviews
  5. Laboratory sample stability. Is it possible to define a consensus stability function? An example of five blood magnitudes
  6. Updated review of postmortem biochemical exploration of hypothermia with a presentation of standard strategy of sampling and analyses
  7. Long non-coding RNA-mediated regulation of signaling pathways in gastric cancer
  8. Opinion Paper
  9. Long story short: an introduction to the short-term and longterm Six Sigma quality and its importance in laboratory medicine for the management of extra-analytical processes
  10. EFLM Paper
  11. The European Federation of Clinical Chemistry and Laboratory Medicine syllabus for postgraduate education and training for Specialists in Laboratory Medicine: version 5 – 2018
  12. General Clinical Chemistry and Laboratory Medicine
  13. Early availability of laboratory results increases same day ward discharge rates
  14. Evaluation of the clinical implementation of a large-scale online e-learning program on venous blood specimen collection guideline practices
  15. Improved prospective risk analysis for clinical laboratories compensated for the throughput in processes
  16. National surveys on internal quality control for blood gas analysis and related electrolytes in clinical laboratories of China
  17. Clinical validation of S100B in the management of a mild traumatic brain injury: issues from an interventional cohort of 1449 adult patients
  18. A quantitative LC-MS/MS method for insulin-like growth factor 1 in human plasma
  19. Development and validation of a mass spectrometry-based assay for quantification of insulin-like factor 3 in human serum
  20. Anti-ganglioside antibodies: experience from the Italian Association of Neuroimmunology external quality assessment scheme
  21. Reference Values and Biological Variations
  22. Improving IBD diagnosis and monitoring by understanding preanalytical, analytical and biological fecal calprotectin variability
  23. Establishing normal values of total testosterone in adult healthy men by the use of four immunometric methods and liquid chromatography-mass spectrometry
  24. Cancer Diagnostics
  25. Exploring the potential of mucin 13 (MUC13) as a biomarker for carcinomas and other diseases
  26. Cardiovascular Diseases
  27. Prognostic implications of detectable cardiac troponin I below the 99th percentile in patients admitted to an emergency department without acute coronary syndrome
  28. Osteocalcin value to identify subclinical atherosclerosis over atherosclerotic cardiovascular disease (ASCVD) risk score in middle-aged and elderly Chinese asymptomatic men
  29. Infectious Diseases
  30. Comparison of four methods of establishing control limits for monitoring quality controls in infectious disease serology testing
  31. Letter to the Editor
  32. Letter to the Editor relative to Clin Chem Lab Med 2018;56(3):360–372
  33. Update in diagnosis and management of primary aldosteronism: reply to a Letter to the Editor
  34. Can calculated total nitrogen replace Kjeldahl total nitrogen measurements in 24-h urine samples?
  35. Analytical performance of the single well titer function of NOVA View®: good enough to omit ANA IIF titer analysis?
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  42. 10th National Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
  43. 5th EFLM-UEMS European Joint Congress in Laboratory Medicine
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