Faecal calprotectin

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Faecal 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[edit]

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[edit]

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, coeliac disease, infectious colitis, necrotizing enterocolitis, intestinal cystic fibrosis and colorectal cancer.[6][7]

Although a relatively new test, faecal calprotectin is regularly used as indicator for inflammatory bowel diseases (IBD) during treatment and as 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 normal in patients with inflammatory bowel disease (IBD).[11] 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]

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]

False-positive measurements[edit]

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.[12] Most importantly, intake of non-steroidal anti-inflammatory drugs (aspirin included) increases calprotectin values, possibly due to the associated induced enteropathy.[13]

References[edit]

  1. ^ a b c Brophy, Megan Brunjes; Nolan, Elizabeth M. (16 January 2015). "Manganese and Microbial Pathogenesis: Sequestration by the Mammalian Immune System and Utilization by Microorganisms". ACS Chemical Biology. 10: 150116125412006. doi:10.1021/cb500792b. 
  2. ^ Marshall, William Marshall,; Lapsley, Marta; Day, Andrew; Ayling, Ruth (2014). Clinical Biochemistry: Metabolic and Clinical Aspects (3 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, Foster R, Sherwood R, Fagerhol M, Bjarnason I (2000). "A simple method for assessing intestinal inflammation in Crohn's disease". Gut. 47 (4): 506–13. PMC 1728060Freely accessible. PMID 10986210. doi:10.1136/gut.47.4.506. 
  5. ^ a b c Joshi S, Lewis SJ, Creanor S, Ayling RM (2009). "Age-related faecal calprotectin, lactoferrin and tumour M2-PK concentrations in healthy volunteers". Annals of Clinical Biochemistry. 47 (Pt 3): 259–263. PMID 19740914. doi:10.1258/acb.2009.009061. 
  6. ^ a b c Vaos G, Kostakis ID, Zavras N, Chatzemichael A (2013). "The role of calprotectin in pediatric disease". Biomed Res Int (Review). 2013: 542363. PMC 3794633Freely accessible. PMID 24175291. doi:10.1155/2013/542363. 
  7. ^ Konikoff MR, Denson LA (Jun 2006). "Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease". Inflamm Bowel Dis (Review). 12 (6): 524–34. PMID 16775498. doi:10.1097/00054725-200606000-00013. 
  8. ^ a b Walsham, Natalie E; Sherwood, Roy A (2016-01-28). "Fecal calprotectin in inflammatory bowel disease". Clinical and Experimental Gastroenterology. 9: 21–29. ISSN 1178-7023. PMC 4734737Freely accessible. PMID 26869808. doi:10.2147/CEG.S51902. 
  9. ^ Stríz, I.; Trebichavský, I. (2004-01-01). "Calprotectin - a pleiotropic molecule in acute and chronic inflammation". Physiological Research / Academia Scientiarum Bohemoslovaca. 53 (3): 245–253. ISSN 0862-8408. PMID 15209531. 
  10. ^ Costa F, Mumolo MG, Bellini M, Romano MR, Ceccarelli L, Arpe P, Sterpi C, Marchi S, Maltinti G (2003). "Role of faecal calprotectin as non-invasive marker of intestinal inflammation". Dig Liver Dis. 35 (9): 642–7. PMID 14563186. doi:10.1016/s1590-8658(03)00381-5. 
  11. ^ Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C, Ricchiuti A, Marchi S, Bottai M (2005). "Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease". Gut. 54 (3): 364–8. PMC 1774401Freely accessible. PMID 15710984. doi:10.1136/gut.2004.043406. 
  12. ^ Waugh N, Cummins E, Royle P, Kandala NB, Shyangdan D, Arasaradnam R, Clar C, Johnston R (Nov 2013). "Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation". Health Technol Assess (Review). 17 (55): xv–xix, 1–211. PMC 4781415Freely accessible. PMID 24286461. doi:10.3310/hta17550. 
  13. ^ Gisbert JP, McNicholl AG (Jan 2009). "Questions and answers on the role of faecal calprotectin as a biological marker in inflammatory bowel disease". Dig Liver Dis (Review). 41 (1): 56–66. PMID 18602356. doi:10.1016/j.dld.2008.05.008. 

See also[edit]