Background/Purpose:  Lack of specific diagnostic, prognostic or response to treatment markers in juvenile idiopathic arthritis (JIA) leads to study new potential markers, as serum calprotectin (S100A8/A9). This heterodimer, part of the S100 protein family, is directly released by activated leukocytes during inflammation, serves as an agonist of TLR4, activates endothelial cells and stimulates transendothelial migration of phagocytes at the site of inflammation. Increased serum calprotectin levels have been described in many inflammatory chronic diseases.To assess the use of serum calprotectin (sCal) as a marker of disease activity and its monitoring, as a classification and prognosis tool of response to treatment or risk of flares in patients with JIA.

Methods:  Ninety-five patients with JIA from the CAP48 multicentric cohort were included in this study (mean age ± SEM: 14,3 ± 0,6 years; F/M sex ratio: 1,4/1; mean disease duration: 2,1 ± 0,6 and 5,0 ± 1,4 years for the newly-diagnosed and well-established JIA respectively), as well as 11 healthy controls (mean age ± SEM: 26,2 ± 0,2; F/M sex ratio: 1,7/1) obtained from the biobank of the Rheumatology department of the Erasme hospital. Enzyme-linked immunosorbent assay (ELISA) method was used to quantify sCal, with a commercial kit. This ELISA had first been adjusted in order to assess the quality of the detection method in sera matrix with spiking recoveries and to elaborate internal positive controls with sera of patients with active Crohn’s disease.

Results:  Patients with inactive JIA had a 4-fold increased level of sCal (6.555 ng/mL) compared to healthy controls (1.737 ng/mL), while patients with active JIA had themselves a 2-fold increased level of sCal (11.403 ng/mL) compared to patients with inactive disease. sCal was found to be slightly correlated to the Tender Joint Count and CHAQ (r/p = 0,2/0,04 and 0,3/0,006 respectively), moderately with the CRP (r/p = 0,2/0,05 and 0,5/0,04 for abnormal values) and strongly with the ESR (r/p = 0,8/0,0003. As for the CRP, sCal could differentiate forms with active oligoarthritis (persistent or extended oligoarthritis or enthesitis-related arthritis) (7.515 ng/mL) from polyarthritis (14.714 ng/mL) or systemic forms (26.976 ng/mL). However, sCal brought an added value compared to the CRP as a prognosis marker. Indeed, patients with active disease had higher serum levels if they were going to be future good-responders (pediACR> 30) at 6 months following the sample test, while patients with inactive disease had higher serum levels if they were going to flare up to 3 to 9 months following the sample test.

Conclusion: This study confirms potential uses of serum calprotectin as a prognosis marker of response to treatment and risk of flares. However, larger studies designed to evaluate sCal in JIA are needed. Attention should also be called in future studies to assess the possible role of sCal in the differential diagnosis of fevers of unknown origin in children.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/calprotectin-as-a-multipotent-biomarker-in-juvenile-idiopathic-arthritis/