Calprotectin is a neutrophil granulocyte-derived protein that has been found in increased levels in plasma, cerebrospinal fluid, synovial fluid, saliva and urine following infection, inflammation and malignant disease in relevant organs, following activation of monocytes and neutrophil granulocytes.
The protein is also excreted in feces, in which it remains very stable, and so fecal calprotectin concentrations may provide an easy test for assessing infection, disease or inflammatory activity in the alimentary tract.
Calprotectin is known to be an inhibitor of zinc-dependent enzymes that, by competing for zinc, can kill microbes and induce apoptosis in both normal and malignant cells.
Zinc-dependent metalloproteinases are needed for activation of cytokines like tumor necrosis factor alpha and for invasive growth of tumors and so it is thought that calprotectin may therefore participate in the regulation of inflammatory processes and inhibit cancer cell proliferation.
However, it is possible that elevated concentrations of this protein may also induce cell and tissue damage.
It is known that there is accumulation of neutrophils at sites of active inflammatory bowel disease (IBD), leading to the possibility that cytotoxic levels of calprotectin may be reached locally and that this protein may also play an active role in IBD, in addition to being a useful fecal marker.
Therefore, researchers from the departments of Gastroenterology and Clinical Biochemistry at the North Manchester General Hospital in Manchester, England, have assessed the potential of measuring calprotectin in feces as a method of screening for alimentary inflammation and neoplasia.
Consented patients attending for routine endoscopy were requested to provide feces.
Of the initial 30 patients enrolled, 17 provided feces before and 1 week after endoscopy.
A further 116 patients with planned endoscopy provided feces prior to undergoing endoscopy.
The group comprised 43 patients with upper gastrointestinal lesions, 7 patients with IBD, a further 7 patients with irritable bowel disease, 31 patients with colonic disorders, and 28 normal people.
A final 18 patients with known inflammatory bowel disease (7 patients), gastric carcinoma (1 patient), colorectal cancer (8 patients) and colorectal adenoma (2 patients) also had stool samples analyzed.
| Fecal calprotectin:|
Elevated in inflammation and cancer
| European Journal of Gastroenterology & Hepatology |
Feces were analyzed using enzyme-linked immunosorbent assay (ELISA) techniques.
Following such analysis, no definite differences between pre- and post-endoscopy calprotectin were found.
Analyses of samples from subsequent patients were therefore carried out on pre-endoscopy feces only, as this was considered preferable.
Upper-gastrointestinal disorders showed little difference in calprotectin levels: Barrett's esophagus (median 6.8 mg/l), gastric ulcer (median 6.5 mg/l) or gastritis/duodenitis (median 5.2 mg/l).
However, these were all higher than the median calprotectin level of normal subjects (4.5 mg/l).
The esophageal and gastric carcinoma median was elevated significantly at 30 mg/l, while inflammatory bowel disease was also associated with marked elevation (Crohn's disease, 31.2 mg/l; ulcerative colitis, 116.2 mg/l).
Colorectal polyps (median 3.7 mg/l) and adenoma (median 3.8 mg/l) showed no elevated levels in contrast to colorectal carcinoma (median 53.4 mg/l).
The elevated calprotectin in IBD and colorectal carcinoma combined gave a sensitivity of 81.8% and a specificity of 73.2%.
"Calprotectin levels are elevated in inflammation and cancer but are not helpful in differentiating between these disorders," commented Dr Christopher B. Summerton, one of the study authors, adding, "In our series, calprotectin was not elevated in colonic polyps or adenomata."
"However," he continued, "Calprotectin could be helpful as a screening method in a general gastroenterology population for inflammatory bowel disease and those with carcinoma, as well as assessing and monitoring disease activity in inflammatory bowel disease."