Calprotectin (CALPR) is a family of calcium-binding S-100 leucocyte proteins with antimicrobial properties [1]. Human CALPR is a dimer of S100A8 and S100A9 proteins. It has antimicrobial and antifungal properties because of its ability to sequester zinc, manganese and iron. It controls intracellular pathways of innate immune cells to produce inflammation [1].

It is a major contributor of cytosolic proteins of neutrophils, though it is found in lower concentration in cytosol of monocytes, macrophages and squamous epithelial cells [1]. It may be further inducible during periods of inflammation. Due to death of neutrophils, high concentrations are seen in pus. However, mechanism of its release in extracellular space during inflammation is not yet clear [1].

Over last 4 decades, fecal CALPR has been used as a sensitive biomarker for inflammatory bowel disease (IBD), even though its specificity is very low [1]. It has also been used as a marker of disease activity in patients with IBD. Elevated serum or tissue CALPR levels have been seen in many inflammatory conditions; however, it can be raised in many conditions with underlying inflammation such as infections, malignancies, diabetes and obesity [1].

First description of elevated serum CALPR levels in juvenile idiopathic arthritis (JIA) was way back in 1991 by Berntzen et al. [2]. They showed that serum CALPR levels had a stronger correlation with clinical and laboratory markers of disease activity compared to other inflammatory markers such as erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Frosch et al. observed higher synovial fluid CALPR levels than serum levels in JIA, concluding thereby that this protein is released locally in the joint by the inflammatory cells [3]. Further it has been studied as a marker to predict relapse in patients who are in remission on therapy [4].

In this issue of the journal, Remthangpuii et al. have evaluated serum CALPR levels in fifty children with treatment-naïve JIA [5]. They found highly raised serum CALPR levels in all subtypes of JIA and showed a positive correlation with disease activity score (JADAS27) and CRP. They did not find significant difference in levels among various subtypes of JIA, even though the study was not adequately powered to look at this aspect. This is in contrast to previous studies where highest levels of serum CALPR were seen in systemic JIA patients followed by polyarthritis and oligoarthritis [6, 7].

In conclusion, only fecal calprotectin has found its role in clinical practice as a sensitive diagnostic and monitoring biomarker in IBD till date. Further studies are required before serum CALPR is accepted as a monitoring biomarker in JIA. It is unlikely to find its role as a diagnostic biomarker in JIA, considering its nonspecific nature.