Various types of organic diseases in the gastrointestinal tract may cause damage to the intestinal epithelial lining (mucosa layer). Such damage may vary from increased permeability of the mucosa to inflammation and ulcerations. The bowel content is rich in bacteria and other microorganisms releasing substances which may be toxic or chemotactic, i.e. they stimulate leukocytes, in particular polymorphonuclear neutrophilic granulocytes (PMN), to migrate into the gut lumen where they release their contents including antimicrobial substances like Calprotectin. This protein constitutes about 60% of total proteins in the cytoplasm of PMNs and can be reliably estimated in faecal samples stored for up to seven days at ambient temperature.
Calprotectin is a 36 kilodalton calcium and zinc-binding protein, produced by PMNs, monocytes and squamous epithelial cells (except those in normal skin). After binding of calcium, it can resist degradation by leukocytic and microbial enzymes. By competing with different enzymes for limited, local amounts of zinc, Calprotectin can inhibit many zinc-dependent enzymes and thereby kill microorganisms or animal and human cells in culture. Different types of disease, for instance bacterial infections, rheumatoid arthritis and cancer, lead to activation of PMNs and increased levels of Calprotectin in plasma, cerebrospinal fluid, synovial fluid, crevicular fluid, urine or other human materials.
It is of special importance that the concentration of Calprotectin in faeces is correlated with the number of PMNs migrating into the gut lumen, and that it can be detected reliably even in small (less than one gram) random stool samples. Furthermore, organic diseases of the bowel give a strong Calprotectin signal, i.e. elevations are regularly five to several thousand times the upper reference in healthy individuals, indicating intestinal inflammation.
Inflammatory bowel diseases (IBD), i.e. ulcerative colitis and Crohn’s disease, may appear from early childhood to late adulthood and the diagnosis is often delayed due to vague symptoms or reluctance to perform endoscopy and biopsy. The CALPROGOLD calprotectin measurement can contribute to an earlier diagnosis of IBD since the test is usually positive in active IBD.
Functional disorders like irritable bowel syndrome (IBS) do not give increased faecal Calprotectin concentrations, but organic abdominal disorders like IBD do. Patients with organic and functional abdominal disorders may have similar symptoms, and clinical examination alone may not be sufficient to give a specific diagnosis. Further diagnostic procedures are complex, expensive and may expose the patient to pain and other risks. A test for faecal Calprotectin is a simple, non-invasive, inexpensive and objective method that can help selecting patients for additional examination like endoscopy. Abdominal symptoms are very common both in children and adults and a negative result as measured by the CALPROGOLD calprotectin kit can with high probability rule out inflammatory bowel disorders.
Mucosal healing is the optimal goal for IBD treatment, and a test for faecal Calprotectin can tell when this has been achieved. Many IBD patients in clinical remission with normal C-reactive protein (CRP) levels still have on-going inflammation, reflected by increased faecal Calprotectin. Such patients have increased risk of relapse within a few months. If mucosal healing can be achieved, the risk of relapse and need for major abdominal surgery will be reduced. Normalisation of Calprotectin levels means that mucosal healing has been achieved. The risk and severity of side effects to treatment should be balanced against the risk of continued inflammation, severe clinical relapse and complications.
The importance of achieving mucosal healing has been the focus of many scientific reviews and articles.