The importance of fecal calprotectin in the diagnostics and treatment of inflammatory bowel diseases


Authors: J. Letkovský;  T. Hlavatý
Authors‘ workplace: V. interná klinika LF UK a UN Bratislava
Published in: Gastroent Hepatol 2015; 69(1): 43-49
Category: IBD: Review Article
doi: 10.14735/amgh201543

Overview

Calprotectin is a cytosolic protein of neutrophil leukocytes. Its concentration correlates with migration of neutrophiles into intestinal lumen. Therefore it is a reliable marker of intestinal inflammation and it is being used in the diagnosis of inflammatory bowel disease. In recent years, new evidence is emerging of its potential use in monitoring of the disease activity, response to therapy or in predicting the disease relapse. However, the use of calprotectin in these indications is rather limited due to persistent uncertainty concerning cut-off values and intervals of its examination.

Key words:
fecal calprotectin –  inflammatory bowel disease –  ulcerative colitis –  Crohn’s disease

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.


Sources

1. Fagerhol MK. Calprotectin, a faecal marker of organic gastrointestinal abnormality. Lancet 2000; 356(9244): 1783– 1784.

2. Sidler MA, Leach ST, Day AS. Fecal S100A12 and fecal calprotectin as noninvasive markers for inflammatory bowel dis­ease in children. Inflamm Bowel Dis 2008; 14(3): 359– 366.

3. Fagerhol MK, Dale I, Anderson I. Release and quantitation of a leucocyte derived protein (L1). Scand J Haematol 1980; 24: 393– 398.

4. Røseth AG, Schmidt PN, Fagerhol MK. Correlation between faecal excretion of indium‑ 111‑ labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel dis­ease. Scand J Gastroenterol 1999; 34(1): 50– 54.

5. Gisbert JP, McNicholl AG. Questions and answers on the role of faecal calprotectin as a bio­logical marker in inflammatory bowel disease. Dig Liver Dis 2009; 41(1): 56– 66. doi: 10.1016/ j.dld.2008.05.008.

6. Røseth AG, Fagerhol MK, Aadland E et al.Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand J Gastroenterol 1992; 27(9): 793– 798.

7. Lasson A, Stotzer PO, Öhman L et al. The intra‑ individual variability of faecal calprotectin: a prospective study in patients with active ulcerative colitis. J Crohns Colitis 2015; 9(1): 26– 32. doi: 10.1016/ j.crohns.2014.06.002.

8. Naismith GD, Smith LA, Barry SJ et al. A prospective single‑centre evaluation of the intra‑ individual variability of faecal calprotectin in quiescent Crohn‘s disease. Aliment Pharmacol Ther 2013; 37(6): 613– 621. doi: 10.1111/ apt.12221.

9. Moum B, Jahnsen J, Bernklev T. Fecal calprotectin variability in Crohn’s disease.Inflamm Bowel Dis 2010; 16(7): 1091– 1092. doi: 10.1002/ ibd.21136.

10. Von Roon AC, Karamountzos L, Purkayastha S et al. Diagnostic precision of fecal calprotectin for inflammatory bowel dis­ease and colorectal malignancy. Am J Gastroenterol 2007; 102(4): 803– 813.

11. Burri E, Beglinger C. The use of fecal calprotectin as a bio­marker in gastrointestinal disease. Expert Rev Gastroenterol Hepatol 2014; 8(2): 197– 210. doi: 10.1586/ 17474124.2014.869476.

12. Costa F, Mumolo MG, Bellini M et al. Role of faecal calprotectin as non‑invasive marker of intestinal inflammation. Dig Liver Dis 2003; 35(9): 642– 647.

13. Van Rheenen PF, van de Vijver E et al.Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta‑analysis. BMJ 2010; 341: c3369. doi: 10.1136/ bmj.c3369.

14. Henderson P, Anderson NH, Wilson DC. The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease: a systematic review and meta‑analysis. Am J Gastroenterol 2014; 109(5): 637– 645. doi: 10.1038/ ajg.2013.131.

15. Labaere D, Smismans A, Van Olmen Aet al. Comparison of six different calprotectin assays for the assessment of inflam­matory bowel disease. United European Gastroenterol J 2014; 2(1): 30– 37. doi: 10.1177/ 2050640613518201.

16. Tibble J, Teahon K, Thjodleifsson B et al.A simple method for assessing intestinal inflammation in Crohn’s disease. Gut 2000; 47(4): 506– 513.

17. Carroccio A, Iacono G, Cottone M et al. Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children. Clin Chem 2003; 49(6 Pt 1): 861– 867.

18. Wassell J, Dolwani S, Metzner M et al. Faecal calprotectin: a new marker for Crohn’s disease? Ann Clin Biochem 2004; 41(Pt 3): 230– 232.

19. Langhorst J, Elsenbruch S, Koelzer Jet al. Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN‑ elastase, CRP, and clinical indices. Am J Gastroenterol 2008; 103(1): 162– 169.

20. Limburg PJ, Ahlquist DA, Sandborn WJ et al. Fecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhea referred for colonoscopy. Am J Gastroenterol 2000; 95(10): 2831– 2837.

21. Chung‑ Faye G, Hayee B, Maestranzi S et al. Fecal M2‑ pyruvate kinase (M2‑ PK): a novel marker of intestinal inflammation. Inflamm Bowel Dis 2007; 13(11): 1374– 1378.

22. D’Inca R, Dal Pont E, Di Leo V et al. Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease. Int J Colorectal Dis 2007; 22(4): 429– 437.

23. Kaiser T, Langhorst J, Wittkowski H et al. Faecal S100A12 as a non‑invasive marker distinguishing inflammatory bowel disease from irritable bowel syndrome. Gut 2007; 56(12): 1706– 1713.

24. Schröder O, Naumann M, Shastri Y et al. Prospective evaluation of faecal neutrophil‑ derived proteins in identifying intestinal inflammation: combination of parameters does not improve diagnostic accuracy of calprotectin. Aliment Pharmacol Ther 2007; 26(7): 1035– 1042.

25. Schoepfer AM, Trummler M, Seeholzer Pet al. Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies. Inflamm Bowel Dis 2008; 14(1): 32– 39.

26. Schoepfer AM, Trummler M, Seeholzer Pet al. Accuracy of four fecal assays in the diagnosis of colitis. Dis Colon Rectum 2007; 50(10): 1697– 1706.

27. Van Assche G, Dignass A, Panes J et al. The second European evidence‑based Consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. J Crohns Colitis 2010; 4(1): 7– 27. doi: 10.1016/ j.crohns.2009.12.003.

28. Sipponen T, Kärkkäinen P, Savilahti E et al. Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn’s disease and histological findings. Aliment Pharmacol Ther 2008; 28(10): 1221– 1229. doi: 10.1111/ j.1365‑ 2036.2008.03835.x.

29. Jones J, Loftus EV Jr, Panaccione R et al. Relationships between disease activity and serum and fecal bio­markers in patients with Crohn’s disease. Clin Gastroenterol Hepatol 2008; 6(11): 1218– 1224. doi: 10.1016/ j.cgh.2008.06.010.

30. Langhorst J, Elsenbruch S, Koelzer J et al. Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN‑ elastase, CRP, and clinical indices. Am J Gastroenterol 2008; 103(1): 162– 169.

31. Aomatsu T, Yoden A, Matsumoto K et al. Fecal calprotectin is a useful marker for disease activity in pediatric patients with inflammatory bowel disease. Dig Dis Sci 2011; 56(8): 2372– 2377. doi: 10.1007/ s10620‑ 011‑ 1633‑ y.

32. Sipponen T, Savilahti E, Kolho KL et al. 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(1): 40– 46.

33. Sipponen T, Savilahti E, Kärkkäinen P et al. Fecal calprotectin, lactoferrin, and endoscopic disease activity in monitor­ing anti‑TNF‑alpha therapy for Crohn’s disease. Inflamm Bowel Dis 2008; 14(10): 1392– 1398. doi: 10.1002/ ibd.20490.

34. Schoepfer AM, Beglinger C, Straumann A et al. Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn’s disease (SES‑ CD) than CRP, blood leukocytes, and the CDAI. Am J Gastroenterol 2010; 105(1): 162– 169. doi: 10.1038/ ajg.2009.545.

35. Denis MA, Reenaers C, Fontaine F et al. Assessment of endoscopic activity index and bio­logical inflammatory markers in clinically active Crohn’s disease with normal C‑ reactive protein serum level. Inflamm Bowel Dis 2007; 13(9): 1100– 1105.

36. Roseth AG, Aadland E, Jahnsen J et al. Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein. Digestion 1997; 58(2): 176– 180.

37. Langhorst J, Elsenbruch S, Mueller T et al. Comparison of 4 neutrophil‑ derived proteins in feces as indicators of disease activity in ulcerative colitis. Inflamm Bowel Dis 2005; 11(12): 1085– 1091.

38. Schoepfer AM, Beglinger C, Straumann A et al. Ulcerative colitis: correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C‑ reactive protein, and blood leukocytes. Inflamm Bowel Dis 2009; 15(12): 1851– 1858. doi: 10.1002/ ibd.20986.

39. Schoepfer AM, Beglinger C, Straumann A et al. Fecal calprotectin more accurately reflects endoscopic activity of ulcerative colitis than the Lichtiger Index, C‑ reactive protein, platelets, hemoglobin, and blood leukocytes. Inflamm Bowel Dis 2013; 19(2): 332– 341. doi: 10.1097/ MIB.0b013e3182810066.

40. D’Haens G, Ferrante M, Vermeire S et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012; 18(12): 2218– 2224. doi: 10.1002/ ibd.22917.

41. Lobatón T, López‑ García A, Rodríguez‑ Moranta F et al. A new rapid test for fecal calprotectin predicts endoscopic remission and postoperative recur­rence in Crohn’s disease. J Crohns Colitis 2013; 7(12): e641– e651. doi: 10.1016/ j.crohns.2013.05.005.

42. Sipponen T, Kolho KL. Faecal calprotectin in children with clinically quiescent inflammatory bowel disease. Scand J Gastroenterol 2010; 45(7– 8): 872– 877. doi: 10.3109/ 00365521003782389.

43. Saverymuttu SH. Clinical remission in Crohn’s disease –  assessment using faecal 111In granulocyte excretion. Digestion 1986; 33(2): 74– 79.

44. Costa F, Mumolo MG, Ceccarelli L et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn‘s disease. Gut 2005; 54(3): 364– 368.

45. Tibble JA, Sigthorsson G, Bridger S et al. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 2000; 119(1): 15– 22.

46. Gisbert JP, Bermejo F, Pérez‑ Calle JL et al. Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse. Inflamm Bowel Dis 2009; 15(8): 1190– 1198. doi: 10.1002/ ibd.20933.

47. D’Inca R, Dal Pont E, Di Leo V et al. Can calprotectin predict relapse risk in inflammatory bowel disease? Am J Gastroenterol 2008; 103(8): 2007– 2014.

48. Diamanti A, Colistro F, Basso MS et al. Clinical role of calprotectin assay in determining histological relapses in children affected by inflammatory bowel diseases. Inflamm Bowel Dis 2008; 14(9): 1229– 1235. doi: 10.1002/ ibd.20472.

49. Walkiewicz D, Werlin SL, Fish D et al. Fecal calprotectin is useful in predicting disease relapse in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2008; 14(5): 669– 673. doi: 10.1002/ ibd.20376.

50. Kallel L, Ayadi I, Matri S et al. Fecal calprotectin is a predictive marker of relapse in Crohn’s disease involving the colon: a prospective study. Eur J Gastroenterol Hepatol 2010; 22(3): 340– 345. doi: 10.1097/ MEG.0b013e32832bab49.

51. García‑ Sánchez V, Iglesias‑ Flores E, González R et al. Does fecal calprotectin predict relapse in patients with Crohn’s dis­ease and ulcerative colitis? J Crohns Colitis 2010; 4(2): 144– 152. doi: 10.1016/ j.crohns.2009.09.008.

52. De Vos M, Louis EJ, Jahnsen J et al. Consecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy. Inflamm Bowel Dis 2013; 19(10): 2111– 2117. doi: 10.1097/ MIB.0b013e31829b2a37.

53. Naismith GD, Smith LA, Barry SJ et al. A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn‘s disease. J Crohns Colitis 2014; 8(9): 1022– 1029. doi: 10.1016/ j.crohns.2014.01.029.

54. Yamamoto T, Shiraki M, Bamba T et al. Fecal calprotectin and lactoferrin as predictors of relapse in patients with quiescent ulcerative colitis during maintenance therapy. Int J Colorect Dis 2014; 29(4): 485– 491. doi: 10.1007/ s00384‑ 013‑ 1817‑ 3.

55. Satsangi J, Silverberg MS, Vermeire S et al. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006; 55(6): 749– 753.

56. Domènech E, Mañosa M, Lobatón T et al. Optimizing post‑operative Crohn’s disease treatment. Ann Gastroenterol 2014; 27(4): 313– 319.

57. Rutgeerts P, Vermeire S, Van Assche G.Mucosal healing in inflammatory bowel dis­ease: impossible ideal or therapeutic target? Gut 2007; 56(4): 453– 455.

58. Van Assche G, Dignass A, Reinisch W et al. The second European evidence‑based Consensus on the diagnosis and management of Crohn’s disease: special situations. J Crohns Colitis 2010; 4(1): 63– 101. doi: 10.1016/ j.crohns.2009.09.009.

59. Orlando A, Modesto I, Castiglione F et al. The role of calprotectin in predicting endoscopic post‑surgical recurrence in asymptomatic Crohn’s disease: a comparison with ultrasound. Eur Rev Med Pharmacol Sci 2006; 10(1): 17– 22.

60. Wright EK, De Cruz PP, Kamm MA et al. Faecal calprotectin helps determine the need for post‑operative colonoscopy in crohn’s disease. Prospective longitudinal endoscopic validation. Results from the POCER study. J Gastroenterol Hepatol 2013; 28 (Suppl 2): 106.

61. Wright EK, De Cruz P, Gearry R et al. Fecal bio­markers in the diagnosis and monitoring of Crohn‘s disease. Inflamm Bowel Dis 2014; 20(9): 1668– 1677. doi: 10.1097/ MIB.0000000000000087.

62. Montalto M, Gallo A, Santoro L et al. Role of fecal calprotectin in gastrointestinal disorders. Eur Rev Med Pharmacol Sci 2013; 17(12): 1569– 1582.

63. Arnott ID, Watts D, Ghosh S. Review article: is clinical remission the optimum therapeutic goal in the treatment of Crohn’s disease? Aliment Pharmacol Ther 2002; 16(5): 857– 867.

64. Hanai H, Takeuchi K, Iida T et al. Relationship between fecal calprotectin, intestinal inflammation, and peripheral blood neutrophils in patients with active ulcerative colitis. Dig Dis Sci 2004; 49(9): 1438– 1443.

65. Roseth AG, Aadland E, Grzyb K. Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease. Scand J Gastroenterol 2004; 39(10): 1017– 1020.

66. Wagner M, Peterson CG, Ridefelt P et al. Fecal markers of inflammation used as surrogate markers for treatment outcome in relapsing inflammatory bowel disease. World J Gastroenterol 2008; 14(36): 5584– 5589.

67. Kolho KL, Raivio T, Lindahl H et al. Fecal calprotectin remains high during glucocorticoid therapy in children with inflammatory bowel disease. Scand J Gastroenterol 2006; 41(6): 720– 725.

68. Aadland E, Fagerhol MK. Faecal calprotectin: a marker of inflammation throughout the intestinal tract. Eur J Gastroenterol Hepatol 2002; 14(8): 823– 825.

69. Sipponen T, Björkesten CG, Färkkilä M et al. Faecal calprotectin and lactoferrin are reliable surrogate markers of endoscopic response during Crohn‘s disease treatment. Scand J Gastroenterol 2010; 45(3): 325– 331. doi: 10.3109/ 00365520903483650.

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