Fecal Calprotectin — a non-invasive indicator of Inflammatory Bowel Disease

Around 2 million people in Europe suffer from Inflammatory Bowel Diseases (IBD). These include a specific group of diseases, including Crohn’s Disease and Ulcerative Colitis, chronic and incurable diseases of the intestinal tract, characterized by recurrent episodes of inflammation of the gastrointestinal tract.

The symptoms, agonizing, embarrassing and debilitating, are important indicators of the disease’s activity, but they can be subjective and appear very similar to other conditions of functional origin, like Irritable Bowel Syndrome, which makes an accurate diagnosis incredibly difficult.

Endoscopy with biopsy is the method of choice, “the golden standard” of monitoring Intestinal Inflammations. However, a new indicator has recently been introduced in Europe, simple, rapid, sensitive, specific, affordable and non-invasive, for the detection and monitoring of IBD. It is called Calprotectin, a high protein distributed in the organism, carrying calcium and zinc. This protein belongs to the S100 group and is mostly derived from neutrophils. Increased levels of Calprotectin have been consistently detected in the feces of patients with active IBD.

Calprotectin is a 36 kDa protein abundant in the cytoplasm of neutrophils and, to a lesser extent, in the reactive monocytes and macrophages. The known functions of Calprotectin are associated with the defence process through zinc action (it displays antibacterial and antifungal activity). It can be detected in virtually any biological fluids and its concentration is directly correlated with the degree of inflammation in a sample. The plasma levels increase 5 to 40 times in the presence of infectious and inflammatory processes. In stool samples, Calprotectin is shown to be a viable biological marker as it remains especially stable for up to seven days at room temperature and is resistant to proteolytic degradation of the feces.

Intestinal inflammation causes the loss of the barrier function of the intestinal mucosa and the migration of neutrophilic granulocytes through the wall into the intestinal lumen, leading to increased concentration of Calprotectin in the feces. The level of fecal Calprotectin is directly related to the number of neutrophilic granulocytes and other immune cells in the intestinal lumen. As such, Calprotectin concentrations are elevated in Inflammatory Bowel Diseases (IBD) and, to a lesser extent, in other situations such as neoplasias and polyps. Calprotectin levels in feces are approximately 6 times higher than those found in blood, making it a good indicator of intestinal inflammation.

Sensitivity and Specificity

Fecal Calprotectin is a very sensitive and specific indicator of inflammation in the intestinal tract: as it is a top-of-the-line test, a negative result can rule out an inflammatory process, while a positive result may suggest endoscopy as a priority method of diagnosis. Almost 98% of patients with inflammatory bowel diseases such as Crohn’s Disease or ulcerative colitis have a higher level of fecal calprotectin. The specificity of the test is almost 90%.

Disease Activity

Fecal calprotectin is an efficient marker for evaluating the therapeutic effectiveness of mucosal healing and its concentration shows a good correlation with endoscopic and histological findings in inflammatory bowel diseases. Recent studies show that the concentration of fecal calprotectin is able to predict a relapse in Crohn’s disease and ulcerative colitis.

When should medication be used?

• Suspected inflammatory bowel diseases (IBD), such as Crohn’s Disease and ulcerative colitis;
  
• To distinguish irritable bowel diseases from other functional bowel syndromes;
  
• IBD monitoring.

In summary, Fecal Calprotectin displays:

• Ability to distinguish Inflammatory Bowel Disease (IBD) from Irritable Bowel Syndrome (IBS);
  
• High negative predictive value;
  
• Good correlation proportional to the degree of inflammation of the intestinal mucosa;
  
• Drastic reduction when the response to treatment is positive, making it a viable indicator in assessing the efficacy of treatment;
  
• It is also a great indicator of relapse, providing an important warning to adapt the patients’ treatment, reducing the intensity of possible relapses.