Faecal calprotectin
{{Short description|Measurement of calprotectin protein in stool}}
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| purpose =biochemical measurement of the protein calprotectin in the stool
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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. Under a specific clinical scenario, the test may eliminate the need for invasive colonoscopy or radio-labelled white cell scanning.
Structure and function
{{see also|Calprotectin|}}
Calprotectin is a 24 kDa dimer of calcium binding proteins S100A8 and S100A9. The complex accounts for up to 60% of the soluble protein content of the neutrophil cytosol. In vitro studies show that calprotectin has bacteriostatic and fungistatic properties, that arise from its ability to sequester manganese and zinc. Calprotectin has two transition metal 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.{{cite journal | vauthors = Tibble J, Teahon K, Thjodleifsson B, Roseth A, Sigthorsson G, Bridger S, Foster R, Sherwood R, Fagerhol M, Bjarnason I | display-authors = 6 | title = A simple method for assessing intestinal inflammation in Crohn's disease | journal = Gut | volume = 47 | issue = 4 | pages = 506–13 | date = October 2000 | pmid = 10986210 | pmc = 1728060 | doi = 10.1136/gut.47.4.506 }}
Use as a surrogate marker
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!colspan=3| Reference ranges for calprotectin | ||
| Patient age
|Upper limit |Unit | ||
| 2–9 years | 166{{cite journal | vauthors = Joshi S, Lewis SJ, Creanor S, Ayling RM | title = Age-related faecal calprotectin, lactoferrin and tumour M2-PK concentrations in healthy volunteers | journal = Annals of Clinical Biochemistry | volume = 47 | issue = Pt 3 | pages = 259–63 | date = May 2010 | pmid = 19740914 | doi = 10.1258/acb.2009.009061 | s2cid = 5396341 }} | rowspan=3| μg/g of faeces |
| 10–59 years | 51 | |
| ≥ 60 years | 112 |
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 and colorectal cancer.{{cite journal | vauthors = Vaos G, Kostakis ID, Zavras N, Chatzemichael A | title = The role of calprotectin in pediatric disease | journal = BioMed Research International | volume = 2013 | pages = 542363 | date = 2013 | pmid = 24175291 | pmc = 3794633 | doi = 10.1155/2013/542363 | type = Review | doi-access = free }}{{cite journal | vauthors = Konikoff MR, Denson LA | title = Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease | journal = Inflammatory Bowel Diseases | volume = 12 | issue = 6 | pages = 524–34 | date = June 2006 | pmid = 16775498 | doi = 10.1097/00054725-200606000-00013 | s2cid = 17882721 | type = Review | doi-access = free }}
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 of the bowel wall. Crohn's disease and ulcerative colitis are the principal types of inflammatory bowel disease. Inflammatory processes result in an influx of neutrophils into the bowel lumen.{{cite journal | vauthors = Walsham NE, Sherwood RA | title = Fecal calprotectin in inflammatory bowel disease | journal = Clinical and Experimental Gastroenterology | volume = 9 | pages = 21–9 | date = 2016-01-28 | pmid = 26869808 | pmc = 4734737 | doi = 10.2147/CEG.S51902 | doi-access = free }} 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.{{cite journal | vauthors = Stríz I, Trebichavský I | title = Calprotectin - a pleiotropic molecule in acute and chronic inflammation | journal = Physiological Research | volume = 53 | issue = 3 | pages = 245–53 | date = 2004-01-01 | doi = 10.33549/physiolres.930448 | pmid = 15209531 | s2cid = 19989349 | doi-access = free }} Measurement of faecal calprotectin has been shown to be strongly correlated with 111-indium-labelled leucocytes – considered the gold standard measurement of intestinal inflammation.{{cite journal | vauthors = Costa F, Mumolo MG, Bellini M, Romano MR, Ceccarelli L, Arpe P, Sterpi C, Marchi S, Maltinti G | display-authors = 6 | title = Role of faecal calprotectin as non-invasive marker of intestinal inflammation | journal = Digestive and Liver Disease | volume = 35 | issue = 9 | pages = 642–7 | date = September 2003 | pmid = 14563186 | doi = 10.1016/s1590-8658(03)00381-5 }}
Levels of faecal calprotectin are usually normal in patients with irritable bowel syndrome (IBS).{{cite journal|display-authors=6|vauthors=Waugh N, Cummins E, Royle P, Kandala NB, Shyangdan D, Arasaradnam R, Clar C, Johnston R|date=November 2013|title=Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation|url=https://doi.org/10.3310%2Fhta17550|journal=Health Technology Assessment|type=Review|volume=17|issue=55|pages=xv-xix, 1-211|doi=10.3310/hta17550|pmc=4781415|pmid=24286461}}{{Better source needed|reason=The current source is insufficiently reliable (WP:NOTRS).|date=January 2024}} 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) patients, especially those with SARS-CoV-2 fecal shedding.{{cite journal | vauthors = Zerbato V, Di Bella S, Giuffré M, Jaracz AW, Gobbo Y, Luppino D, Macor P, Segat L, Koncan R, D'Agaro P, Valentini M, Crocé LS, Ruscio M, Luzzati R | display-authors = 2 | title = High fecal calprotectin levels are associated with SARS-CoV-2 intestinal shedding in COVID-19 patients: A proof-of-concept study | journal = World Journal of Gastroenterology | volume = 27 | issue = 22 | pages = 3130–3137 | date = June 2021 | pmid = 34168414 | doi = 10.3748/wjg.v27.i22.3130 | pmc = 8192288 | doi-access = free }}
Faecal calprotectin is measured using immunochemical techniques such as ELISA or immunochromatographic assays. The antibodies used in these assays target specific epitopes of the calprotectin molecule.
Increased faecal calprotectin may be indicative of intestinal tuberculosis or pulmonary tuberculosis.{{Cite journal |last1=Larsson |first1=Geir |last2=Shenoy |first2=Koticherry Thrivikrama |last3=Ramasubramanian |first3=Ramalingom |last4=Thayumanavan |first4=Lakshmikanthan |last5=Balakumaran |first5=Leena Kondarappassery |last6=Bjune |first6=Gunnar A |last7=Moum |first7=Bjørn A |date=October 2014 |title=Faecal calprotectin levels differentiate intestinal from pulmonary tuberculosis: An observational study from Southern India |journal=United European Gastroenterology Journal |volume=2 |issue=5 |pages=397–405 |doi=10.1177/2050640614546947 |issn=2050-6406 |pmc=4212497 |pmid=25360318}}
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.{{cite journal | vauthors = Gisbert JP, McNicholl AG | title = Questions and answers on the role of faecal calprotectin as a biological marker in inflammatory bowel disease | journal = Digestive and Liver Disease | volume = 41 | issue = 1 | pages = 56–66 | date = January 2009 | pmid = 18602356 | doi = 10.1016/j.dld.2008.05.008 | url = http://www.dldjournalonline.com/article/S1590-8658%2808%2900191-6/pdf | type = Review | doi-access = free }}
See also
References
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