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Fecal calprotectin as a marker of inflammatory bowel diseases

https://doi.org/10.21508/1027-4065-2023-68-5-138-143

Abstract

Calprotectin is a calcium- and zinc-binding protein belonging to the S100 protein family. This protein is found mainly in the cytoplasm of neutrophils, and, to a lesser extent, in monocytes and macrophages, which can be found in any human organs, but mainly in blood, cerebrospinal fluid, feces, saliva, and synovial fluid. Calprotectin is an effective tool forthe differential diagnosis of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). There is a connection of fecal calprotectin (FC) with the endoscopic activity of IBD, however, the available literature shows significant differences in the sensitivity and specificity of FC for predicting the endoscopic activity of the disease. In addition, FC can be considered as a predictor of histological mucosal healing and as a marker for assessing the response to treatment, including surgical, but there is still no consensus on the threshold value of a biomarker for these purposes. Conflicting data are presented in reports on FC as a predictor of IBD recurrence. FC seems to be effective for detecting relapse, however, there is no specific threshold value, therefore, the marker cannot completely replace endoscopic examination methods. In addition, there is intraindividual variability in the concentration of FC in patients, depending on age, type of feeding in the first year of life, taking medications, which significantly complicates the interpretation of the results.

About the Authors

A. A. Kamalova
Kazan State Medical University
Russian Federation

Kazan



G. A. Garina
Kazan State Medical University
Russian Federation

Kazan



I. Kh. Valeeva
Kazan State Medical University
Russian Federation

Kazan



A. R. Gaifutdinova
Kazan State Medical University
Russian Federation

Kazan



References

1. Naess-Andresen C.F., Egelandsdal B., Fagerhol M.K. Calcium binding and concomitant changes in the structure and heat stability of calprotectin (L1 protein). Clin Mol Pathol 1995; 48: 278–284. DOI: 10.1136/mp.48.5.m278

2. Haisma S.M., van Rheenen P.F., Wagenmakers L., Muller K.A. Calprotectin instability may lead to undertreatment in children with IBD. Arch Dis Child 2019; 105: 1–3. DOI: 10.1136/archdischild-2018–316584

3. Oyaert M., Van den Bremt S., Boel A., Bossuyt X., Van Hoovels L. Do not forget about pre-analytics in faecal calprotectin measurement! Clin Chim Acta 2017; 473:124–126. DOI: 10.1016/j.cca.2017.08.025

4. Roseth A.G., Fagerhol M.K., Aadland E., Schjonsby H. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand J Gastroenterol 1992; 27: 793–798. DOI: 10.3109/00365529209011186

5. Roseth A.G., Aadland E., Jahnsen J., Raknerud N. Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein. Digestion 1997; 58: 176–180. DOI: 10.1159/000201441

6. Levine A., Turner D., Pfeffer Gik T., Amil Dias J., Veres G., Shaoul R. et al. Comparison of outcomes parameters for induction of remission in New Onset Pediatric Crohn’s Disease: evaluation of the Porto IBD Group «Growth Relapse and Outcomes with Therapy» (GROWTH CD) Study. Inflamm Bowel Dis 2014; 20: 278–285. DOI: 10.1097/01.MIB.0000437735.11953.68

7. Degraeuwe P.L., Beld M.P., Ashorn M., Canani R.B., Day A.S., Diamanti A. et al. Faecal calprotectin in suspected paediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2015; 60: 339. DOI: 10.1097/MPG.0000000000000615

8. Khaki-Khatibi F., Qujeq D., Kashifard M., Moein S., Maniati M., Vaghari-Tabari M. Calprotectin in inflammatory bowel disease. Clin Chim Acta 2020; 510: 556–565. DOI: 10.1016/j.cca.2020.08.025

9. Menees S.B., Powell C., Kurlander J., Goel A., Chey W.D. A meta-analysis of the utility of C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and fecal lactoferrin to exclude inflammatory bowel disease in adults with IBS. Am J Gastroenterol 2015; 110: 444–454. DOI: 10.1038/ajg.2015.6

10. Clinical recommendations of the Ministry of Health of the Russian Federation. Ulcerative colitis. Approved by the Ministry of Health of the Russian Federation in 2021. Approved by the Scientific and Practical Council of the Ministry of Health of the Russian Federation. 2021: 17. (in Russ.)

11. Roseth A.G., Aadland E., Grzyb K. Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease. Scand J Gastroenterol 2004; 39: 1017–1020. DOI: 10.1080/00365520410007971

12. Sipponen T., Savilahti E., Kolho K.L., Nuutinen H., Turunen U., Färkkilä M. Crohn’s disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn’s disease activity index and endoscopic findings. Inflamm Bowel Dis 2008; 14: 40–46. DOI: 10.1002/ibd.20312

13. Vieira A., Fang C.B., Rolim E.G., Klug W.A., Steinwurz F., Rossini L. et al. Inflammatory bowel disease activity assessed by fecal calprotectin and lactoferrin: correlation with laboratory parameters, clinical, endoscopic and histological indexes. BMC Res Notes 2009; 2: 221. DOI: 10.1186/1756–0500–2–221

14. Melmed G.Y., Dubinsky M.C., Rubin D.T., Fleisher M., Pasha S.F., Sakuraba A. et al. Utility of video capsule endoscopy for longitudinal monitoring of Crohn’s disease activity in the small bowel: a prospective study. Gastrointest Endosc 2018; 88: 947–955. DOI: 10.1016/j.gie.2018.07.035

15. Egea Valenzuela J., Pereñíguez López A., Pérez Fernández V., Alberca de Las Parras F., Carballo Álvarez F. Fecal calprotectin and C-reactive protein are associated with positive findings in capsule endoscopy in suspected small bowel Crohn’s disease. Rev Esp Enferm Dig 2016; 108: 394–400. DOI: 10.17235/reed.2016.4318/2016

16. Theede K., Holck S., Ibsen P., Ladelund S., Nordgaard-Lassen I., Nielsen A.M. Level of fecal calprotectin correlates with endoscopic and histologic inflammation and identifies patients with mucosal healing in ulcerative colitis. Clin Gastroenterol Hepatol 2015; 13: 1929–1936. DOI: 10.1016/j.cgh.2015.05.038

17. Walsh A., Kormilitzin A., Hinds C., Sexton V., Brain O., Keshav S. et al. Defining faecal calprotectin thresholds as a surrogate for endoscopic and histological disease activity in ulcerative colitis-a prospective analysis. J Crohns Colitis 2019; 13: 424–430. DOI: 10.1093/ecco-jcc/jjy184

18. Molander P., af Björkesten C.G., Mustonen H., Haapamäki J., Vauhkonen M., Kolho K.L. et al. Fecal calprotectin concentration predicts outcome in inflammatory bowel disease after induction therapy with TNFalpha blocking agents. Inflamm Bowel Dis 2012; 18: 2011–2017. DOI: 10.1002/ibd.22863

19. Hamalainen A., Sipponen T., Kolho K.L. Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels. World J Gastroenterol 2011; 17: 5166–5171. DOI: 10.3748/wjg.v17.i47.5166

20. Sipponen T., Kolho K. Faecal calprotectin in children with clinically quiescent inflammatory bowel disease. Scand J Gastroenterol 2010; 45: 872–877. DOI: 10.3109/00365521003782389

21. Amil-Dias J., Kolacek S., Turner D., Pærregaard A., Rintala R., Afzal N.A. et al. IBD Working Group of ESPGHAN (IBD Porto Group). Surgical management of Crohn disease in children: guidelines from the paediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr 2017; 64: 818–835. DOI: 10.1097/MPG.0000000000001562

22. Tibble J.A., Sigthorsson G., Bridger S., Fagerhol M.K., Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 2000; 119: 15–22. DOI: 10.1053/gast.2000.8523

23. Costa F., Mumolo M.G., Ceccarelli L., Bellini M., Romano M.R., Sterpi C. et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut 2005; 54: 364–368. DOI: 10.1136/gut.2004.043406

24. Laharie D., Mesli S., El Hajbi F., Chabrun E., Chanteloup E., Capdepont M. et al. Prediction of Crohn’s disease relapse with faecal calprotectin in infliximab responders: a prospective study. Aliment Pharmacol Ther 2011; 34: 462–469. DOI: 10.1111/j.1365–2036.2011.04778.x

25. Hart L., Chavannes M., Kherad O., Maedler C., Mourad N., Marcus V. et al. Faecal calprotectin predicts endoscopic and histological activity in clinically quiescent ulcerative colitis. J Crohns Colitis 2019; 14: 46– 52. DOI: 10.1093/ecco-jcc/jjz107

26. Li J., Zhao X., Li X., Lu M., Zhang H. Systematic review with meta-analysis: fecal calprotectin as a surrogate marker for predicting relapse in adults with ulcerative colitis. Mediators Inflamm 2019; 28: 11. DOI: 10.1155/2019/2136501

27. Ruemmele F.M., Veres G., Kolho K.L., Griffiths A., Levine A., Escher J.C. et al. European Crohn’s and Colitis Organisation, European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Consensus guidelines of ECCO/ ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis 2014; 8: 1179–1207. DOI: 10.1016/j.crohns.2014.04.005

28. van Rheenen P.F., Aloi M., Assa A., Bronsky J., Escher J.C., Fagerberg U.L. et al. The medical management of paediatric Crohn’s disease: an ECCO-ESPGHAN Guideline Update. J Crohn’s Colitis 2020; 15: 171–194. DOI: 10.1093/ecco-jcc/jjaa161

29. Kolho K., Alfthan H. Concentration of fecal calprotectin in 11,255 children aged 0–18 years. Scand J Gastroenterol 2020; 55: 1024–1027. DOI: 10.1080/00365521.2020.1794026

30. Turner D., Ruemmele F.M., Orlanski-Meyer E., Griffiths A.M., de Carpi J.M., Bronsky J. et al. Management of paediatric ulcerative colitis, part 2: acute severe colitis — an evidence-based Consensus Guideline From the European Crohn’s and Colitis Organization and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018; 67: 292–310. DOI: 10.1097/MPG.0000000000002036

31. Moum B., Jahnsen J., T. Bernklev. Fecal calprotectin variability in Crohn’s disease. Inflamm Bowel Dis 2010; 16: 1091–1092. DOI: 10.1002/ibd.21136

32. Meling T.R., Aabakken L., Røseth A., Osnes M. Faecal calprotectin shedding after short-term treatment with non-steroidal anti-inflammatory drugs. Scand J Gastroenterol 1996; 31: 339–344. DOI: 10.3109/00365529609006407

33. Poullis A., Foster R., Mendall M.A., Shreeve D., Wiener K. Proton pump inhibitors are associated with elevation of faecal calprotectin and may affect specificity. Eur J Gastroenterol Hepatol 2003; 15: 573–574. DOI: 10.1097/00042737–200305000–00021

34. Kolho K. L., Alfthan H., Hamalainen E. Effect of bowel cleansing for colonoscopy on fecal calprotectin levels in pediatric patients. J Pediatr Gastroenterol Nutr 2012; 55: 751–753. DOI: 10.1097/MPG.0b013e31825f4c77

35. Alibrahim B., Aljasser M.I., Salh B. Fecal calprotectin use in inflammatory bowel disease and beyond: a mini-review. Can J Gastroenterol Hepatol 2015; 29: 157–163. DOI: 10.1155/2015/950286

36. Fagerberg U.L., Lööf L., Merzoug R.D., Hansson L.O., Finkel Y. Fecal calprotectin levels in healthy children studied with an improved assay. J Pediatr Gastroenterol Nutr 2003; 37: 468–472. DOI: 10.1097/00005176–200310000–00013

37. Olafsdottir E., Aksnes L., Fluge G., Berstad A. Faecal calprotectin levels in infants with infantile colic, healthy infants, children with inflammatory bowel disease, children with recurrent abdominal pain and healthy children. Acta Paediatr 2002; 91: 45–50. DOI: 10.1080/080352502753457932

38. Zoppelli L., Güttel C., Bittrich H.J., Andrée C., Wirth S., Jenke A. Fecal calprotectin concentrations in premature infants have a lower limit and show postnatal and gestational age dependence. Neonatology 2012; 102: 68–74. DOI: 10.1159/000337841

39. Josefsson S., Bunn S. K., Domellof M. Fecal calprotectin in very low birth weight infants. J Pediatr Gastroenterol Nutr 2007; 44: 407–413. DOI: 10.1097/MPG.0b013e3180320643

40. Kapel N., Campeotto F., Kalach N., Baldassare M., Butel M.J., Dupont C. Faecal calprotectin in term and preterm neonates. J Pediatr Gastroenterol Nutr 2010; 51: 542–547. DOI: 10.1097/MPG.0b013e3181e2ad72

41. Koninckx C.R., Donat E., Benninga M.A., Broekaert I.J., Gottrand F., Kolho K.L. et al. The Use of Fecal Calprotectin Testing in Paediatric Disorders: A Position Paper of the European Society for Paediatric Gastroenterology and Nutrition Gastroenterology Committee. J Pediatr Gastroenterol Nutr 2021; 72: 617–640. DOI: 10.1097/MPG.0000000000003046

42. Velasco Rodríguez-Belvís M., Viada Bris J.F., Plata Fernández C., García-Salido A., Asensio Antón J., Domínguez Ortega G. et al. Normal fecal calprotectin levels in healthy children are higher than in adults and decrease with age. Paediatrics Child Health 2019; 25: 286–292. DOI: 10.1093/pch/pxz070


Review

For citations:


Kamalova A.A., Garina G.A., Valeeva I.Kh., Gaifutdinova A.R. Fecal calprotectin as a marker of inflammatory bowel diseases. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2023;68(5):138-143. (In Russ.) https://doi.org/10.21508/1027-4065-2023-68-5-138-143

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ISSN 1027-4065 (Print)
ISSN 2500-2228 (Online)