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

Emma Altobelli,Reimondo Petrocelli,Luciana Breda,Giovanni Farello,Giuseppe Lapergola,Giovanni Cannataro,Paolo Matteo Angeletti

doi:10.3390/jcm10214861

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.

Highlights

Juvenile idiopathic arthritis (JIA) is the most common autoimmune/inflammatory chronic disease affecting children and adolescents
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]
One the current unsolved problem in pediatric rheumatology is identifying predictive markers of disease activity, therapeutic response, and relapse upon discontinuation of treatment. This is the first systematic review with a meta-analysis evaluating the role of serum CLP as a possible predictor marker in the management of JIA

Summary

Introduction

Juvenile idiopathic arthritis (JIA) is the most common autoimmune/inflammatory chronic disease affecting children and adolescents. JIA comprises a heterogeneous group of joint diseases with distinct clinical phenotypes, disease courses, and outcomes. It is known that JIA can be associated with morbidity and mortality and represents a cause of short-term and long-term disability. The epidemiology is variable worldwide with incidence rates ranging from 1.6 to 23/100.000 [1,2]. In the past two decades, there have been important therapeutic advances in the management of JIA, to date, we are not yet able to predict the course of the disease, the therapeutic response, and relapses after drug discontinuation. There is a great need for biomarkers to guide clinical decisions such as starting, switching, or tapering methotrexate or biologic DMARDs [3]

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