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Serum Calprotectin a Potential Biomarker in Juvenile Idiopathic Arthritis: A Meta-Analysis
Emma Altobelli1, Paolo Matteo Angeletti1,2, Reimondo Petrocelli3
1Department of Life, Public Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Insights
Serum calprotectin (CLP) shows promise as a biomarker for juvenile idiopathic arthritis (JIA) activity. Elevated CLP levels differentiate active JIA from inactive disease and healthy controls, aiding in disease stratification.
Area of Science:
- Pediatric Rheumatology
- Biomarker Discovery
- Inflammatory Diseases
Background:
- Juvenile idiopathic arthritis (JIA) is a prevalent chronic inflammatory condition in children and adolescents.
- Current diagnostic and monitoring approaches for JIA lack specific inflammatory biomarkers.
- Identifying novel biomarkers is crucial for accurately assessing JIA disease activity.
Purpose of the Study:
- To systematically review and meta-analyze the potential role of calprotectin (CLP) as a biomarker in JIA.
- To evaluate CLP's utility in differentiating disease activity states within JIA.
- To assess CLP levels in JIA patients compared to healthy controls.
Main Methods:
- A comprehensive literature search was performed across major scientific databases (PubMed, EMBASE, Scopus, Science Direct) following PRISMA 2020 guidelines.
- Effect sizes were calculated using Cohen's d with 95% CI and p-values.
- Random effects models, Q statistics, I² for heterogeneity, and Egger's test for publication bias were employed.
Main Results:
- Serum CLP levels were significantly higher in patients with active JIA compared to those with inactive disease (p=0.001).
- A significant difference in CLP concentration was observed between systemic JIA and inactive disease forms (p<0.001).
- Serum CLP was significantly elevated in JIA patients compared to healthy controls, with lower levels in the control group.
Conclusions:
- Serum calprotectin (CLP) demonstrates potential as a valuable tool for stratifying JIA disease activity.
- CLP may facilitate a more personalized treatment approach for children with JIA.
- Further research is warranted to explore CLP's predictive value for disease flares and its combination with other biomarkers.
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.
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