Faecal calprotectin (
or fecal calprotectin) is a
biochemical measurement of the protein
calprotectin in the
stool. Elevated faecal calprotectin indicates the migration of
neutrophils to the intestinal
mucosa, which occurs during intestinal inflammation, including inflammation caused by
inflammatory bowel disease
Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...
. Under a specific clinical scenario, the test may eliminate the need for invasive
colonoscopy
Colonoscopy () or coloscopy () is a medical procedure involving the Endoscopy, endoscopic examination of the large bowel (colon) and the distal portion of the small bowel. This examination is performed using either a Charge-coupled device, CCD ...
or radio-labelled
white cell scanning.
Structure and function
Calprotectin is a 24 kDa
dimer of
calcium
Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
binding proteins
S100A8 and
S100A9.
The complex accounts for up to 60% of the soluble protein content of the
neutrophil
Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
.
''
In vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
'' studies show that calprotectin has
bacteriostatic and
fungistatic properties, that arise from its ability to sequester
manganese
Manganese is a chemical element; it has Symbol (chemistry), symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese was first isolated in the 1770s. It is a transition m ...
and
zinc
Zinc is a chemical element; it has symbol Zn and atomic number 30. It is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic tabl ...
.
Calprotectin has two
transition metal
In chemistry, a transition metal (or transition element) is a chemical element in the d-block of the periodic table (groups 3 to 12), though the elements of group 12 (and less often group 3) are sometimes excluded. The lanthanide and actinid ...
binding sites that form at the interface of the S100A8 and S100A9 monomers, and metal sequestration by calprotectin has been shown to be calcium dependent.
The complex is resistant to
enzymatic degradation, and can be easily measured in
faeces
Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...
.
Use as a surrogate marker
The main diseases that cause an increased excretion of faecal calprotectin are
inflammatory bowel diseases (IBD),
coeliac disease,
infectious colitis,
necrotizing enterocolitis in infants, intestinal
cystic fibrosis
Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
and
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...
.
Although a relatively new test, faecal calprotectin is regularly used as indicator for IBD during treatment and as a diagnostic marker.
IBD are a group of conditions that cause a
pathological inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
of the
bowel wall.
Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...
and
ulcerative colitis
Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...
are the principal types of inflammatory bowel disease. Inflammatory processes result in an influx of neutrophils into the bowel
lumen.
Since calprotectin comprises as much as 60% of the soluble protein content of the cytosol of neutrophils, it can serve as a marker for the level of intestinal inflammation. Measurement of faecal calprotectin has been shown to be strongly correlated with 111-
indium
Indium is a chemical element; it has Symbol (chemistry), symbol In and atomic number 49. It is a silvery-white post-transition metal and one of the softest elements. Chemically, indium is similar to gallium and thallium, and its properties are la ...
-labelled
leucocytes – considered the gold standard measurement of
intestinal inflammation.
Levels of faecal calprotectin are usually normal in patients with
irritable bowel syndrome
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating, and changes in the consistency of bowel movements. These symptoms may ...
(IBS).
In untreated coeliac disease, concentration levels of faecal calprotectin correlate with the degree of
intestinal mucosal lesion and normalize with a
gluten-free diet.
High fecal calprotectin is a common finding among hospitalized coronavirus disease 2019 (
COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic.
The symptoms of COVID‑19 can vary but often include fever ...
) patients, especially those with
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...
fecal shedding.
Faecal calprotectin is measured using
immunochemical techniques such as
ELISA
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
or
immunochromatographic assays. The
antibodies
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
used in these assays target specific
epitopes of the calprotectin molecule.
Increased faecal calprotectin may be indicative of intestinal tuberculosis or pulmonary tuberculosis.
False-positive measurements
Although faecal calprotectin correlates significantly with disease activity in people with confirmed IBD, faecal calprotectin can be false-positive if the laboratory uses low calprotectin cut-off levels.
[ Most importantly, intake of non-steroidal anti-inflammatory drugs (aspirin included) increases calprotectin values, possibly due to the associated induced enteropathy.]
See also
* Calgranulin
References
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Diagnostic gastroenterology