Calprotectin, formed as a heterodimer of S100A8 and S100A9, is a member of the S100 calcium-binding protein family. It is expressed primarily by granulocytes and, to a lesser degree, by monocytes/macrophages and epithelial cells. In neutrophils, calprotectin comprises almost 60% of the total cytoplasmic protein content. Activation of the intestinal immune system leads to recruitment of cells from the innate immune system, including neutrophils. The neutrophils are then activated, which leads to release of cellular proteins, including calprotectin. Calprotectin eventually translocates across the epithelial barrier and enters the lumen of the gut. As the inflammatory process progresses, the released calprotectin is absorbed by the fecal material before it is excreted from the body. The amount of calprotectin present in the feces is proportional to the number of neutrophils within the gastrointestinal mucosa and can be used as an indirect marker of intestinal inflammation.
Calprotectin is most frequently used as part of the diagnostic evaluation of patients with suspected inflammatory bowel disease (IBD). Patients with IBD may be diagnosed with Crohn disease or ulcerative colitis. Although distinct in their pathology and clinical manifestations, both are associated with significant intestinal inflammation. Elevated concentrations of fecal calprotectin may be useful in distinguishing IBD from functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). When used for this differential diagnosis, fecal calprotectin has sensitivity and specificity both of approximately 85%. However, it must be remembered that increases in fecal calprotectin are not diagnostic for IBD, as other disorders such as celiac disease, colorectal cancer, and gastrointestinal infections, may also be associated with neutrophilic inflammation.