Circulating calprotectin in paediatrics: Benefits and clinical applications

Calprotectin - Emerging biomarker for multiple paediatric diseases

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.

Clinical utility of calprotectin in paediatric rheumatology

Predicting flares in Juvenile Idiopathic Arthritis (JIA)

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

Diagnosis of Still’s disease

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

Monitoring disease activity in Vasculitis (Kawasaki Disease and IgAV)

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 in differentiation between bacterial and viral infections

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

Clinical value of circulating calprotectin in paediatric disease management

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.

GCAL® - plasma and serum calprotectin

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References: 

1. La C et al. Serum calprotectin (S100A8/A9): a promising biomarker in diagnosis and follow-up in different subgroups of juvenile idiopathic arthritis. RMD Open. 2021
2. Altobelli E et al. Serum Calprotectin a Potential Biomarker in Juvenile Idiopathic Arthritis: A Meta-Analysis. J Clin Med. 2021
3. Foell Det al. Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial. JAMA. 2010
4. Sumner EJ et al. Use of MRP8/14 in clinical practice as a predictor of outcome after methotrexate withdrawal in patients with juvenile idiopathic arthritis. Clin Rheumatol. 2022
5. d'Angelo DM et al. Serum calprotectin and joint ultrasound in the definition of disease relapse in non-systemic juvenile idiopathic arthritis: a prospective longitudinal study. Clin Exp Rheumatol. 2024
6. Anink J et al. MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis. Arthritis Res Ther. 2015
7. Park C et al. MRP8/14 serum levels as diagnostic markers for systemic juvenile idiopathic arthritis in children with prolonged fever. Rheumatology (Oxford). 2022
8. Fautrel B et al. EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease. Ann Rheum Dis. 2024
9. Srsen S et al. Serum Levels of S100A8/A9 as a Biomarker of Disease Activity in Patients with IgA Vasculitis. Biomedicines. 2024
10. Hirono K et al. Expression of myeloid-related protein-8 and -14 in patients with acute Kawasaki disease. J Am Coll Cardiol. 2006
11. Lech M et al. Circulating Markers of Inflammation Persist in Children and Adults With Giant Aneurysms After Kawasaki Disease. Circ Genom Precis Med. 2019
12. Hoshino S et al. Biomarkers of inflammation and fibrosis in young adults with history of Kawasaki disease. Int J Cardiol Heart Vasc, 2021
13. Lamot M et al. Serum Calprotectin Is a Valid Biomarker in Distinction of Bacterial Urinary Tract Infection From Viral Respiratory Illness in Children Under 3 Years of Age. Front Pediatr. 2022
14. Bohn MK et al. Validation of Serum Calprotectin Relative to Other Biomarkers of Infection in Febrile Infants Presenting to the Emergency Department. Antibiotics (Basel). 2024
15. Xie S et al. Serum level of S100A8/A9 as a biomarker for establishing the diagnosis and severity of community-acquired pneumonia in children. Front Cell Infect Microbiol. 2023

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