Biological functions and clinical significance of calprotectin. Review

Abstract

Recently, in addition to clinical, endoscopic and morphological studies, the algorithm for the diagnosis of inflammatory bowel disease (IBD) also includes some serum and fecal biomarkers that help select patients for endoscopy, as well as distinguish between organic and functional (non‑inflammatory) diseases (for example, irritable bowel syndrome). Among the latter, the definition of fecal calprotectin (CP) is used mostly often, it is a well‑studied biomarker of inflammation due to its stability, reproducibility of analysis, low cost, and high diagnostic value. The presented review highlights the latest data on the main biological CP functions and the clinical application of its definition in inflammatory diseases of intestine, skin, joints, etc.
 It is shown that CP belongs to the family of calcium‑binding leukocyte S100 proteins and consists of two monomers: S100A8 and S100A9. CP is constitutively expressed by monocytes, dendritic cells, activated macrophages, keratinocytes of the oral cavity and squamous epithelium of the mucosa. Thus, the CP expression in a healthy person is limited by a small number of specialized cells and is usually activated during inflammation. Both subunits of CP, S100A8 and S100A9, have a wide range of intracellular and extracellular immunomodulatory properties, control the intracellular pathways of innate immune cells and are responsible for organizing the response to the inflammatory process.
 Determination of fecal CP enables distinguishing between non‑inflammatory and inflammatory bowel diseases, it is a non‑invasive inexpensive method, and the CP itself remains stable at room temperature in the feces for at least 3 days. In the diagnosis of IBD, fecal CP is a more sensitive marker than C‑reactive protein, which has made it an excellent (i.e., highly sensitive) biomarker for detecting intestinal inflammation in IBD and has contributed to its widespread use worldwide. The value of the level of fecal Cp < 40 mg/g can reliably exclude IBD, and a value > 250 mg/g dictates the need for endoscopic examination of the patient for IBD or raises the suspicion of its recurrence.