Serum Calprotectin (S100A8/A9): A Promising Biomarker in Diagnosis and Follow-up in Different Subgroups of Juvenile Idiopathic Arthritis

Abstract

BackgroundManagement of juvenile idiopathic arthritis (JIA) lacks of diagnostic and prognostic biomarkers. Therefore, this study was designed to assess the use of serum calprotectin (sCal) as a marker of disease activity and its monitoring, and as a classification and prognosis tool of response to treatment or risk of flares in patients with JIA. MethodsEighty-one patients with JIA from the CAP48 multicentric cohort were included in this study, as well as 11 healthy controls. Enzyme-linked immunosorbent assay (ELISA) method was used to quantify sCal with a commercial kit. Mann-Whitney tests were used to compare results, correlations were assessed with Spearman’s rank correlation coefficients and Receiver Operating Characteristic curves were also generated to evaluate serum calprotectin as a prognostic tool.ResultsPatients with an active disease compared to healthy controls and to patients with inactive disease showed an 8-fold and a 2-fold increased level of sCal respectively. sCal was found to be correlated with the CRP and even more strongly with the ESR. Evolution of DAS28 scores correlated well with evolution of sCal, as opposed to evolution of CRP. As for the CRP, sCal could differentiate forms with active oligoarthritis from polyarthritis or systemic forms. However, sCal brought an added value compared to the CRP as a prognosis marker. Indeed, patients with active disease and good responder to treatment (pediACR > 30) at 6 months following the sample test had higher sCal levels, while patients with inactive disease had higher sCal levels in case a flare was observed up to 3 to 9 months following the sample test.ConclusionsThis study confirms the potential uses of serum calprotectin as a biomarker in diagnosis and follow-up in JIA.

Serum Calprotectin a Potential Biomarker in Juvenile Idiopathic Arthritis: A Meta-Analysis

“…Among these, Barendreght et al [9] enrolled naive patients stratified into two groups (Table S1). Our results at follow-up showed a statistically significant difference between patients with active disease compared to patients with inactive disease: 0.39 (0.16; 0.62), p = 0.001; without statistical heterogeneity (Table 1, Figure 5) [9][10][11][12][13]. Later, we stratified the six studies with respect to therapy at baseline.…”

“…Eight of the 10 studies compared active versus inactive disease (pauci-articular and polyarticular forms) [ 6 , 8 , 9 , 10 , 11 , 12 , 13 ]. In particular, one study considered two different groups of patients with different duration of disease, and they enrolled in two different times [ 9 ].…”

“…Their comparison at baseline shows that there are serum calprotectin differences between patients with active and inactive disease: 0.27 (0.08;0.47), p < 0.005; without statistical heterogeneity ( Table 1 , Figure 2 ). However, when selecting patients based on therapy status, there are no statistically significant differences between active and inactive patients: 0.16 (−0.03: 0.40), p = 0.104; without statistical heterogeneity ( Table 1 , Figure 2 ) [ 8 , 9 , 10 , 11 , 12 , 13 ]. Meta-regression analyses performed on gender, age, duration of disease, percentage of patients with ANA+ or RF+, medium value of ESR or CRP were not statistically significant ( Table 2 ).…”

“…Of all studies included in the meta-analysis, four reported the comparison of serum calprotectin levels among patients suffering from any form of JIA versus healthy controls [ 5 , 6 , 7 , 8 , 11 ] ( Table 1 , Figure 4 ). Although two studies compared adult subjects [ 5 , 8 ], the results showed a statistically significant difference: 0.72 (0.42; 1.01), p < 0.001; without statistical heterogeneity ( Table 1 , Figure 4 ).…”

“…Recently, some researchers have directed their interest toward a protein, calprotectin (CLP), as a potential biomarker for disease activity [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ].…”