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- Serum calprotectin as a biomarker for diagnosis and monitoring of juvenile idiopathic arthritis - a systematic reviewPublication . Horta, Mariana Pereira; Guerra, Miguel Gomes; Oliveira, Margarida Isabel Dias AlexandreIntroduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is characterized by clinical, pathophysiological, and prognostic heterogeneity. Its etiology remains unclear and, according to the International League of Associations for Rheumatology (ILAR) criteria, encompasses seven distinct subtypes, defined by clinical manifestations. The lack of specific biomarkers hinders early diagnosis, subtype stratification, and monitoring of inflammatory activity, which is often subclinical. Serum calprotectin (sCal), a protein of the calgranulin family produced by activated neutrophils and monocytes, has emerged as a direct marker of synovial inflammation, demonstrating superiority over classic parameters such as C-reactive protein (CRP) and sedimentation rate (ESR). Objective: To carry out a systematic review of the literature, aiming to clarify the role of sCal as a biomarker in the diagnosis and monitoring of JIA, exploring its value in clinical practice and follow-up of these patients. Methods: A systematic search of the PubMed and EMBASE databases was conducted until January 2025, according to the PRISMA 2020 recommendations. Observational studies and clinical trials that analysed sCal in patients with JIA were included, excluding case reports/series, experimental studies in animals, and articles with fewer than 20 participants. Selection was performed by independent reviewers, with discrepancies resolved by consensus. Risk of bias was assessed using tools from the National Heart, Lung, and Blood Institute (NHLB). Data extracted included population characteristics, laboratory parameters, and main outcomes related to diagnosis and monitoring. Results: A total of 639 publications were identified, of which 38 met the inclusion criteria. Overall, sCal levels were significantly higher in children with JIA compared with healthy controls, with better performance in differentiating the systemic form. There was a consistent correlation with clinical activity scores (e.g., JADAS, DAS28), confirming its usefulness in disease monitoring. Several studies have demonstrated the predictive value of sCal in response to different therapies and in predicting relapses after treatment discontinuation. However, the lack of uniform cutoffs and methodological heterogeneity limited comparability between studies. Conclusions: This review confirms the role of sCal as a biomarker with the potential to complement the clinical evaluation of JIA, both in diagnosis and monitoring. The results suggest advantages over traditional markers, particularly in correlation with inflammatory activity and in supporting therapeutic decision-making. However, its integration into routine clinical practice requires validation in robust studies that establish standardized cut-offs and laboratory protocols.