Faecal calprotectin

Faecal calprotectin
Purposebiochemical measurement of the protein calprotectin in the stool

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.[1] The complex accounts for up to 60% of the soluble protein content of the neutrophil cytosol.[2][3] In vitro studies show that calprotectin has bacteriostatic and fungistatic properties, that arise from its ability to sequester manganese and zinc.[1] 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.[1] The complex is resistant to enzymatic degradation, and can be easily measured in faeces.[4]

Use as a surrogate marker

Reference ranges for calprotectin
Patient age Upper limit Unit
2–9 years 166[5] μg/g of faeces
10–59 years 51[5]
≥ 60 years 112[5]

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.[6][7]

Although a relatively new test, faecal calprotectin is regularly used as indicator for IBD during treatment and as a diagnostic marker.[6] 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.[8] 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.[9] Measurement of faecal calprotectin has been shown to be strongly correlated with 111-indium-labelled leucocytes – considered the gold standard measurement of intestinal inflammation.[10]

Levels of faecal calprotectin are usually normal in patients with irritable bowel syndrome (IBS).[11][better source needed] In untreated coeliac disease, concentration levels of faecal calprotectin correlate with the degree of intestinal mucosal lesion and normalize with a gluten-free diet.[6] High fecal calprotectin is a common finding among hospitalized coronavirus disease 2019 (COVID-19) patients, especially those with SARS-CoV-2 fecal shedding.[12]

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.[8]

Increased faecal calprotectin may be indicative of intestinal tuberculosis or pulmonary tuberculosis.[13]

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.[11] Most importantly, intake of non-steroidal anti-inflammatory drugs (aspirin included) increases calprotectin values, possibly due to the associated induced enteropathy.[14]

See also

References

  1. ^ a b c Brophy MB, Nolan EM (March 2015). "Manganese and microbial pathogenesis: sequestration by the Mammalian immune system and utilization by microorganisms". ACS Chemical Biology. 10 (3): 641–51. doi:10.1021/cb500792b. PMC 4372095. PMID 25594606.
  2. ^ Marshall W, Lapsley M, Day A, Ayling R (2014). Clinical Biochemistry: Metabolic and Clinical Aspects (3rd ed.). Elsevier Health Sciences, 2014. ISBN 9780702054785. Retrieved 19 January 2015.
  3. ^ Gupta, Ramesh (2014). Biomarkers in toxicology. San Diego, CA: Academic Press. pp. 272–273. ISBN 9780124046498. Retrieved 19 January 2015.
  4. ^ Tibble J, Teahon K, Thjodleifsson B, Roseth A, Sigthorsson G, Bridger S, et al. (October 2000). "A simple method for assessing intestinal inflammation in Crohn's disease". Gut. 47 (4): 506–13. doi:10.1136/gut.47.4.506. PMC 1728060. PMID 10986210.
  5. ^ a b c Joshi S, Lewis SJ, Creanor S, Ayling RM (May 2010). "Age-related faecal calprotectin, lactoferrin and tumour M2-PK concentrations in healthy volunteers". Annals of Clinical Biochemistry. 47 (Pt 3): 259–63. doi:10.1258/acb.2009.009061. PMID 19740914. S2CID 5396341.
  6. ^ a b c Vaos G, Kostakis ID, Zavras N, Chatzemichael A (2013). "The role of calprotectin in pediatric disease". BioMed Research International (Review). 2013: 542363. doi:10.1155/2013/542363. PMC 3794633. PMID 24175291.
  7. ^ Konikoff MR, Denson LA (June 2006). "Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease". Inflammatory Bowel Diseases (Review). 12 (6): 524–34. doi:10.1097/00054725-200606000-00013. PMID 16775498. S2CID 17882721.
  8. ^ a b Walsham NE, Sherwood RA (2016-01-28). "Fecal calprotectin in inflammatory bowel disease". Clinical and Experimental Gastroenterology. 9: 21–9. doi:10.2147/CEG.S51902. PMC 4734737. PMID 26869808.
  9. ^ Stríz I, Trebichavský I (2004-01-01). "Calprotectin - a pleiotropic molecule in acute and chronic inflammation". Physiological Research. 53 (3): 245–53. doi:10.33549/physiolres.930448. PMID 15209531. S2CID 19989349.
  10. ^ Costa F, Mumolo MG, Bellini M, Romano MR, Ceccarelli L, Arpe P, et al. (September 2003). "Role of faecal calprotectin as non-invasive marker of intestinal inflammation". Digestive and Liver Disease. 35 (9): 642–7. doi:10.1016/s1590-8658(03)00381-5. PMID 14563186.
  11. ^ a b Waugh N, Cummins E, Royle P, Kandala NB, Shyangdan D, Arasaradnam R, et al. (November 2013). "Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation". Health Technology Assessment (Review). 17 (55): xv–xix, 1–211. doi:10.3310/hta17550. PMC 4781415. PMID 24286461.
  12. ^ Zerbato V, Di Bella S, et al. (June 2021). "High fecal calprotectin levels are associated with SARS-CoV-2 intestinal shedding in COVID-19 patients: A proof-of-concept study". World Journal of Gastroenterology. 27 (22): 3130–3137. doi:10.3748/wjg.v27.i22.3130. PMC 8192288. PMID 34168414.
  13. ^ Larsson, Geir; Shenoy, Koticherry Thrivikrama; Ramasubramanian, Ramalingom; Thayumanavan, Lakshmikanthan; Balakumaran, Leena Kondarappassery; Bjune, Gunnar A; Moum, Bjørn A (October 2014). "Faecal calprotectin levels differentiate intestinal from pulmonary tuberculosis: An observational study from Southern India". United European Gastroenterology Journal. 2 (5): 397–405. doi:10.1177/2050640614546947. ISSN 2050-6406. PMC 4212497. PMID 25360318.
  14. ^ Gisbert JP, McNicholl AG (January 2009). "Questions and answers on the role of faecal calprotectin as a biological marker in inflammatory bowel disease". Digestive and Liver Disease (Review). 41 (1): 56–66. doi:10.1016/j.dld.2008.05.008. PMID 18602356.