Serum calprotectin may reflect inflammatory activity in patients with active rheumatoid arthritis despite normal to low C-reactive protein
Approximately half of patients with rheumatoid arthritis (RA) have normal C-reactive protein (CRP) levels. Calprotectin is a promising and likely more specific biomarker of disease activity than conventionally used acute phase reactants. We aimed to analyse the levels of serum calprotectin in RA patients with clinically active disease and with normal/low CRP. A total of 160 RA patients underwent clinical examination (DAS28-ESR and CDAI). The levels of calprotectin were analysed in patients with moderate to high disease activity with normal/low CRP levels and in 32 healthy subjects. The discriminatory capacity of calprotectin to identify clinically active patients in spite of normal/low CRP was assessed using ROC curves. Out of all RA patients, 74/160 (46.3%) were in remission or had low disease activity according to DAS28 and had normal/low CRP levels. However, 51/160 (32%) had normal/low CRP levels despite having moderate to high disease activity. In these patients, calprotectin levels were significantly higher than those in patients who had normal/low CRP and were in remission or showed low disease activity (2.7 ± 1.5 vs. 2.1 ± 1.2 μg/mL, p = 0.043), which differed from those in healthy subjects (2.7 ± 1.5 vs. 1.9 ± 1.2 μg/mL, p = 0.011). The discriminatory capacity for calprotectin to distinguish clinically active vs. inactive disease despite normal/low CRP using AUC of the DAS28 was 0.607 (95% CI 0.503 to 0.711, p = 0.043). The present study demonstrates that calprotectin may reflect inflammatory activity in RA patients where CRP fails to do so.
KeywordsCalprotectin C-reactive protein Inflammation Rheumatoid arthritis
anti-cyclic citrullinated peptide antibody
area under the curve
Clinical Disease Activity Index
Disease Activity Score for 28 joints with erythrocyte sedimentation rate
enzyme-linked immunosorbent assay
erythrocyte sedimentation rate
receiver operating curves
swollen joint count
tender joint count
visual analogue scale
JH was the principal investigator for the study, participated in the data analysis and interpretation and prepared the first draft of the manuscript. HH and LAC were responsible for the quantification of calprotectin and the manuscript revision. JZ and HM participated in the data analysis and interpretation and revised the manuscript. MK performed statistical analysis, participated in the data interpretation and helped draft the manuscript. JV revised the manuscript critically for important intellectual content. KP facilitated the performance of the study and revised the manuscript. LS participated in the study design, facilitated the performance of the study and revised the final draft of the paper. All authors have read and approved the final manuscript.
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication.
This work was supported by a project of the Ministry of Health of the Czech Republic for conceptual research development by organisation  and Specific Academy Research Projects (SVV) .
Compliance with ethical standards
The study was performed according to the Declaration of Helsinki and was approved by the local ethics committee of the Institute of Rheumatology in Prague (Reference number 3560/2010).
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