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Increased calprotectin – What do high calprotectin values mean?

Dr. med. Andre Sommer

Dr. med. Andre Sommer

Increased calprotectin – What do high calprotectin values mean?

Calprotectin is a biomarker that can be detected in stool when there is inflammation of the intestine. The marker is not specific for a specific disease, but may be increased in acute infections as well as in inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. An increased calprotectin value can help differentiate between an organic cause of abdominal discomfort and a functional cause such as irritable bowel syndrome. There are also other causes of increased calprotectin.

What is calprotectin?

Calprotectin is also called human leukocyte protein. It is a small particle inside certain immune system cells, the so-called neutrophil granulocytes. Even if it is not yet completely clear what calprotectin does there, it is assumed that it protects the immune cell against its own active agents. When inflamed, immune cells release substances that can break down harmful cells, such as invading bacteria. So that the immune cells do not self-decompose in this way, they have built in several security mechanisms, which probably include calprotectin. In addition, calprotectin has a direct antimicrobial effect and can thus support the immune cells in the fight against pathogens.

What is calprotectin used for?

With an inflammation in the intestine, immune cells as part of the immune system are lured into the intestinal wall by tissue hormones. They are supposed to fight possible pathogens there. The presence of immune cells in chronic bowel inflammation can be taken advantage of by doctors. They measure the number of immune cells in the stool and determine whether there is inflammation in the intestine. Since the immune cells in stool are not so easy to measure, only one specific biomarker is measured instead of the whole cell: calprotectin.

The more immune cells in the stool, the more calprotectin can also be detected. It therefore provides an indirect indication of the inflammatory activity in the intestine. This is useful for the distinction of whether abdominal discomfort is due to an organic cause, for example a chronic inflammatory bowel disease, or due to a functional cause such as irritable bowel syndrome. In addition, calprotectin is also used as a progression parameter in chronic inflammation.

How is calprotectin measured?

Calprotectin is determined in stool samples, preferably in the first bowel movement of the day. Since the protein does not break down, it can still be detected after days. The stool sample does not have to be cooled for this. In the laboratory, the stool specimen is mixed with special antibodies, which attach to the calprotectin and mark it in color. This procedure is called ELISA (Enzyme-linked Immunosorbent Assay). The more color is visible in the sample, the more calprotectin it contains. The amount is given in micrograms (µg) per gram (g) of stool.

Healthy people without inflammation in the intestine have a calprotectin value less than 50 µg / g in the stool, newborns show elevated values up to 250 µg / g, without this having to have a pathological meaning. It is believed that these values come about because the intestines of an infant are constantly colonized in the first year of life by new bacteria that later become part of the normal intestinal flora.

What are the causes of increased calprotectin?

Increased calprotectin indicates that inflammation is taking place in the intestine. Calprotectin is a so-called unspecific bio marker because it cannot be used to diagnose a specific disease (e.g. ulcerative colitis or Crohn's disease). That is why it is always important to include the subjective symptoms and physical findings in the diagnosis. Diagnosis based only on a calprotectin value is not possible.

Gastrointestinal infections

If the calprotectin value is increased, for example, a viral or bacterial gastrointestinal infection may be present. This is particularly likely if you suddenly experience vomiting, abdominal pain and diarrhea.

Intestinal inflammation

If symptoms such as abdominal pain, nausea, feeling of fullness and diarrhea have existed for a long time, an inflammatory bowel disease could be at the base of an increased calprotectin value. The two main representatives of this group are ulcerative colitis and Crohn's disease. The calprotectin values are then significantly above the normal values. Most of the time, they also increase when those affected go through an episode of illness. In the course of these diseases, the value is also used to check the success of anti-inflammatory therapy.

Colorectal cancer and diverticulosis

Tumors cause inflammation so the calprotectin level is elevated with cancer. Here, too, the value gives no indication of the type and stage of a tumor. The most widespread diverticular disease also leads to increased calprotectin values and sometimes shows similar symptoms such as abdominal pain, digestive problems, blood in the stool and occasional fever.

Diseases of the upper digestive system

The focus of calprotectin determination is on the detection of inflammation in the intestine. However, since the food porridge has already passed through the esophagus and stomach, the inflammation there can also increase the values. This can be the case for gastritis, a stomach ulcer or esophagitis.

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In which diseases is the calprotectin level not increased?

Many diseases lead to similar symptoms in the intestine: Abdominal pain, feeling of fullness, constipation, gas and diarrhea are not just signs of inflammation. Also food intolerances and celiac disease (an autoimmune reaction of the body to the grain protein gluten) or lactose intolerance can trigger such symptoms. For example, if the pancreas does not produce enough digestive enzymes due to chronic inflammation, this also leads to diarrhea and abdominal pain. Last but not least, irritable bowel syndrome may be responsible for many complaints without a disturbance in the intestine being proven. The calprotectin level is not increased in all these diseases. So it offers the chance to get a rough approximation of a diagnosis without a painful or complicated intervention, but only with a stool sample. This makes the procedure particularly useful in the treatment of children.


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Which additional examinations should be carried out?

In addition to a detailed medical consultation (anamnesis) and the physical examination, the calprotectin determination is a building block for diagnosis. Depending on how the first calprotectin value turns out, additional examinations must follow in order to find out the diagnosis in detail. Because acute infections cause the values to rise, a stool sample is usually done to search for bacteria, viruses and toxins.

If the value is increased without a pathogen being detected, the next step is usually a colonoscopy. A camera is inserted into the colon via the rectum. Signs of inflammation can often be detected directly on this camera. Tissue samples (Biopsies) are also taken and later examined under a microscope. Tumors or tumor precursors can also be discovered with this examination. If inflammation is more likely in the upper gastrointestinal tract, an esophagogastroduodenoscopy can be used to examine this part of the digestive tract in more detail.

What to do if the calprotectin level is not increased?

For example, if the calprotectin level is not elevated, tests for food intolerance and other causes can be carried out. Most of the time, it is recommended to avoid the suspect food for a while and observe the symptoms. If the symptoms disappear under this diet and reappear after the new introduction of the food, this is usually sufficient as evidence. There are also other blood tests for celiac disease and a tissue sample should be taken from the duodenum during an examination. If these diseases are excluded, it may ultimately be a case of irritable bowel syndrome.

How secure is a diagnosis based on the calprotectin value?

As already mentioned, a laboratory value is not synonymous with a diagnosis, especially if it is an unspecific marker. However, the calprotectin value can predict the absence of inflammation very well. That means that if the calprotectin value is in the normal range, with a high probability,no inflammation is present. Therefore, diseases such as ulcerative colitis and Crohn's disease can be excluded with a relatively high probability.

Things get more inaccurate when the values are slightly above the norm: Inflammation may be present here, but need not be. The value cannot show what kind of inflammation it is. Calprotectin is also too imprecise for cancer detection and is therefore not used as a screening method for all people.

Does an increased calprotectin level need to be treated?

Calprotectin itself is not dangerous for the body and therefore does not necessarily have to be lowered. It should instead be considered as a warning that further investigations are necessary. If the cause of the inflammation has been found and possibly treated, the calprotectin value in the stool will also decrease. It can therefore, to a certain extent, be used as a “success meter” for the therapy.

Medizinisches Labor Bremen: Lactoferrin und Calprotectin im Stuhl. 2016. http://www.mlhb.de/fileadmin/userupload/Startseite/Service/Laborinformationen/LactoferrinCalprotectinStuhluntersuchung270116.pdf, 15/08/2016

Carroccio, Antonio, et al. Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children. Clinical chemistry, 2003, 49. Jg., Nr. 6, S. 861-867. http://www.clinchem.org/content/49/6/861.full, 15/08/2016

Summerton, Christopher B., et al. Faecal calprotectin: a marker of inflammation throughout the intestinal tract. European journal of gastroenterology & hepatology, 2002, 14. Jg., Nr. 8, p 841-845.

Fagerberg, Ulrika Lorentzon, et al. Colorectal inflammation is well predicted by fecal calprotectin in children with gastrointestinal symptoms. Journal of pediatric gastroenterology and nutrition, 2005, 40. Jg., Nr. 4, p 450-455.

Lundberg, Jon O., et al. Technology insight: calprotectin, lactoferrin and nitric oxide as novel markers of inflammatory bowel disease. Nature Clinical Practice Gastroenterology & Hepatology, 2005, 2. Jg., Nr. 2, p 96-102.

Dr. med. Andre Sommer

Dr. med. Andre Sommer

I’m André, a medical doctor from Berlin. Together with a team of medical doctors, nutritionists and data scientists we empower people to understand digestive issues with our app Cara Care.

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