Calprotectin, a calcium-binding protein complex of S100A8 and S100A9, is primarily expressed by neutrophils and plays a crucial role in the body's innate immune response and inflammation. Known for its antimicrobial properties and signalling in inflammation, circulating calprotectin is increasingly recognised as a valuable biomarker in various inflammatory conditions, like rheumatoid arthritis, as well as infections due to its role in the inflammatory reaction upon bacterial infections.
Corresponding circulating calprotectin has been described as emerging biomarker for multiple paediatric diseases. This article explores the benefits and clinical applications of circulating calprotectin in paediatrics, highlighting its role in improving diagnostic, treatment plans and patient outcomes.
Juvenile Idiopathic Arthritis (JIA) is one of the primary conditions where calprotectin has shown significant clinical utility. Circulating calprotectin levels correlate with disease activity and can be used to monitor treatment response and predict disease flares.1,2 Unlike traditional biomarkers like CRP and ESR, which may not always reflect active disease, calprotectin offers a more sensitive measure of inflammation. The outstanding sensitivity of calprotectin shows particular importance in states of low disease activity, like the determination of true immunological remission.
Calprotectin's ability to predict flares provides clinicians with a powerful tool to manage treatment plans more effectively, potentially allowing for safer withdrawal of medications in patients who achieve inactive disease. 3-6
Still’s disease (formerly Systemic JIA (sJIA)) presents unique diagnostic challenges, particularly in differentiating it from systemic infections. Circulating calprotectin levels are significantly higher in active sJIA compared to infections, offering high diagnostic sensitivity and specificity which has been reported up to 73% and 90% respectively.7
This makes calprotectin an invaluable marker for distinguishing Still’s disease from other febrile conditions, guiding appropriate treatment decisions. This strong support in diagnosis of Still’s has been endorsed by the EULAR and PReS in 2024 and incorporated into the recommendations on the management of Still’s disease.8
In childhood vasculitis, Kawasaki disease (KD) and IgA vasculitis, circulating calprotectin levels have been shown to correlate with disease activity, suggesting its potential use in monitoring these conditions.9,10 Specifically, in KD, elevated calprotectin levels indicate ongoing inflammation and are associated with the development of coronary artery aneurysms. This highlights calprotectin's role in identifying patients at risk of long-term complications and guiding long-term management strategies.11,12
Calprotectin has also proven effective in differentiating bacterial from viral infections in young children, a critical distinction for appropriate treatment.13,14 Thereby calprotectin can give substantial added value in the early management of a child with fever as an accurate biomarker in distinction between bacterial and viral infection.
Additionally, circulating calprotectin levels correlate with the severity of conditions like community-acquired pneumonia (CAP), offering a higher diagnostic efficacy compared to traditional markers and important guidance in patient management.15
The emerging evidence underscores calprotectin's value as a versatile biomarker in paediatric diseases. Its ability to provide early and accurate insights into disease activity, treatment response, and the risk of flares makes it an indispensable tool in paediatric rheumatology and beyond. As research continues to evolve, calprotectin's role in clinical practice is likely to expand, offering enhanced patient care and more targeted therapeutic approaches.
Gentian’s calprotectin immunoassay, GCAL®, is the first turbidimetric assay for the quantitative measurement of calprotectin in plasma and serum, used as an aid in detection and assessment of inflammation and inflammatory response to infections.
With a rapid turnaround time of just 10 minutes, GCAL® provides fast and reliable results on a wide range of automated clinical chemistry analysers. The assay is CE-marked and IVDR-certified, ensuring high quality and regulatory compliance for clinical use.*
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