Summarizing the Biological Function and Current Clinical Understanding of Calprotectin

Investigators reviewed the recent research on the biological function of calprotectin in inflammatory diseases.

A review article published in Gut summarized the current literature regarding the role of calprotectin (CP) in gut health. An established clinical biomarker of inflammatory bowel diseases (IBD), CP also demonstrates immunomodulatory properties and may be a key component in the pathology of chronic inflammatory conditions. Improved understanding of CP biology could allow for the development of novel therapies and interventions for IBD and other inflammatory conditions, authors wrote. 

First described in the 1980s, CP is a calcium-binding S100 leucocyte protein comprised of 2 monomers: S100A8 and S100A9. The S100A8/S100A9 complex has been implicated in many immunomodulatory pathways and appears to trigger neutrophil chemotaxis and endothelial adhesion. CP may also play a role in the proliferation of tumor cells, epithelial cells, and smooth muscle cells. The specific activities of the individual subunits remain unclear. Further studies involving knock-out mice may serve to elucidate the biological functions of S100A8 and S100A9.

As a biomarker, fecal CP can be used to discriminate between noninflammatory and inflammatory intestinal disease. High fecal CP levels (>600 μg/g) are associated with IBD and food-borne infections, though no clinical cut-off values have been established. CP levels also appear to reflect disease activity, with higher concentrations indicating more severe disease. Some studies have demonstrated that fecal CP can be used to distinguish between patients with active ulcerative colitis (UC) and patients in remission. Again, however, a validated cut-off level has not been established and studies used varying target values of CP in their research.

Recent studies indicate that CP may also have utility as a biomarker in inflammatory diseases beyond the gut, including psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and certain cancers. Systemic inflammation in psoriatic arthritis can be detected through serum CP levels, per the results of 1 study. However, serum CP is also linked to systemic low-grade inflammation, as with obesity or type 2 diabetes, indicating poor specificity for other inflammatory diseases.

The investigators stated, “We propose that a better understanding of the biological functions of CP and particularly the S100A8 and S100A9 subunits will lead to novel diagnostic and therapeutic advances in humans in the future,” investigators wrote. “Translation of biological insights by mechanistic studies of mucosal surfaces in mice to human disease is scarce, but would evolve our understanding of CP as inflammatory biomarker,” they concluded.

Reference

Jukic A, Bakiri L, Wagner EF, Tilg H, Adolph TE. Calprotectin: from biomarker to biological function. Gut. Published online June 28, 2021. doi:10.1136/gutjnl-2021-324855