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Pre-analytical and analytical confounders of serum calprotectin as a biomarker in rheumatoid arthritis

  • Lieve Van Hoovels EMAIL logo , Bert Vander Cruyssen , Laura Bogaert , Stefanie Van den Bremt and Xavier Bossuyt
Published/Copyright: October 30, 2019

Abstract

Background

There is a need for additional biomarkers to assist in the diagnosis and prognosis of rheumatoid arthritis (RA). The aim of our study was to evaluate the (pre-analytical, analytical and clinical) performance of serum calprotectin as a marker of inflammation in RA.

Methods

The study population included 463 rheumatologic patients (including 111 RA patients and 352 controls) who for the first time consulted a rheumatologist, 20 healthy controls and 27 patients with an infectious disease. Calprotectin was measured (using four different assays) in serum or in serum and EDTA plasma (healthy controls and infectious disease group). For rheumatologic patients, results for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were available.

Results

Results for blood calprotectin were assay- and matrix-dependent, with higher values found in serum than in plasma. Serum calprotectin was higher in RA patients than in rheumatologic diseased controls and in healthy controls. Serum calprotectin was lower in RA patients than in patients with an infectious disease. Serum calprotectin was associated with disease activity (DAS score). The area under the curve (AUC) to discriminate RA from controls was 0.756 for CRP, 0.714 for ESR and 0.726–0.783 for calprotectin.

Conclusions

Our data document that calprotectin measurement is assay- and matrix-dependent. Serum calprotectin is associated with disease activity. Additional (prospective) studies are warranted to further evaluate the prognostic and diagnostic value of blood calprotectin measurements.

Acknowledgments

We thank Bühlmann, Diasorin, Inova Diagnostics and Thermo Fisher for the donation of the assays and the constructive discussion of the results. Furthermore, we acknowledge Prof. Jörg Steinmann of Labor Dr. Fenner und Kollegen (Hamburg) for providing the R&D protocol of the EliA calprotectin 2 analysis. Finally, we are very thankful to Dr. Julie Jacobs for her work regarding the patient cohort categorization and to the laboratory technicians for their most appreciated efforts regarding the practical work.

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

  2. Research funding: None declared.

  3. Employment or leadership: XB has been consultant for Inova Diagnostics and Thermo Fisher Scientific.

  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-2019-0508).


Received: 2019-05-20
Accepted: 2019-09-15
Published Online: 2019-10-30
Published in Print: 2019-12-18

©2020 Walter de Gruyter GmbH, Berlin/Boston

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