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

Abstract

Juvenile idiopathic arthritis (JIA) is the most common inflammatory chronic disease affecting children and adolescents. Today, there are no specific biomarkers of inflammation. Therefore, it is important to identify new markers as predictors of disease activity. Recently, some researchers have directed their interest toward a protein, calprotectin (CLP), as a potential biomarker. The primary objective of our systematic review and meta-analysis was to analyze the possible role of CLP in JIA. Method: A literature search was conducted using PubMed, EMBASE, Scopus, Science Direct on 10 August 2021. The selection of studies was made using the PRISMA 2020 guidelines. Cohen’s d with 95% CI and p-value were used as a measure of effect size. The random effects model was used to account for different sources of variation among studies. Heterogeneity was assessed using Q statistics and I2. The publication bias was analyzed and represented by a funnel plot, and funnel plot symmetry was assessed with Egger’s test. Results: 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. Another important aspect that emerged were the differences between the systemic disease form and any form of inactive disease showing a different concentration of calprotectin: 0.74 (0.40; 1.08), p < 0.001; without statistical heterogeneity. On the other hand, 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. A statistically significant difference in serum calprotectin concentration between patients with JIA and healthy controls were observed. In fact, it presented lower values in the control group. Conclusions: The use of serum CLP could represent, in the future, a useful tool in JIA in order to stratify disease activity more accurately and may aid a more tailored approach to drug of choice in children with JIA. Further studies are needed to evaluate CLP as a predictor of flare in combination with other potential biomarkers of subclinical disease activity.

The Role of Serum Calprotectin in Defining Disease Outcomes in Non-Systemic Juvenile Idiopathic Arthritis: A Pilot Study

“…In this prospective longitudinal study, the first finding was that serum calprotectin levels, at baseline, were significantly higher in active patients than in controls and inactive patients, are were further increased with disease activity. In addition, we found that serum calprotectin values correlated strongly with JADAS27 and did not correlate with CRP, ESR, ANA and RF, nor with gender, age or disease duration of patients with JIA, partially in contrast with some previous reports [ 25 , 26 , 27 ]. In contrast with conventional markers of inflammation, which reflect the acute phase response mediated by hepatocytes or B lymphocytes during inflammation, calprotectin seems to provide additional information on the state of disease in JIA children.…”

“…A meta-analysis and systemic review was recently published including 10 specific studies on the pediatric population. Altobelli et al [ 27 ] confirmed that the use of serum calprotectin represents a useful tool in JIA in order to stratify disease activity in JIA children; however, the extreme heterogeneity of the JIA populations studied, especially in terms of treatment, did not allow further conclusive data. In addition, Hurnakova et al [ 28 ] showed that in RA patients, serum calprotectin was the best predictor of ultrasound synovitis, performing better than CRP.…”

Expanded population of low-density neutrophils in juvenile idiopathic arthritis

“…However, it cannot be excluded that in vivo LDNs are primed and that they subsequently become more susceptible to other stimuli. JIA LDN percentage positively correlated with serum calprotectin levels, a potential marker for diagnosis, prediction of disease relapse, response to treatment and risk of flares in JIA and other autoimmune diseases, such as RA, SLE and inflammatory bowel disease ( 41 – 43 ). Calprotectin is released mostly by phagocyting cells such as neutrophils at the site of inflammation, where it can modulate inflammatory response ( 44 ).…”

Diagnostic Accuracy Study of the Pediatric‐Specific Ultrasound Scoring System for the Knee Joint in Children With Juvenile Idiopathic Arthritis

“…Biomarkers were chosen based on reports of detection in serum and synovial fluid of JIA and RA patients. [20][21][22][23][24] S100 proteins, cytokine, and chemokine measurements were performed by the CCHMC Research Flow Cytometry Core. S100A8/A9 concentrations were determined by enzyme-linked immunosorbent assay using Pro-cartaPlex kits from ThermoFisher Scientific according to the manufacturer's directions.…”