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Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease

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Abstract

Background and aims

Calprotectin and lactoferrin are specific neutrophil-derived proteins, which can be measured in the feces because they are released by cells in inflammatory conditions. We evaluated the efficacy of calprotectin and lactoferrin in detecting organic disease as assessed by colonoscopy.

Methods

The study comprised 144 patients undergoing colonoscopy for lower gastrointestinal symptoms (abdominal pain, altered bowel habits, and bloody stools) (67), or inflammatory bowel disease activity, or surveillance for dysplasia (77). A single stool sample was assayed for calprotectin and lactoferrin. The proportion of patients correctly diagnosed with each test and the relationship with endoscopic and histological findings were measured.

Results

Fecal excretion of calprotectin significantly correlated with the finding of colonic inflammation at endoscopy, both in ulcerative colitis and in Crohn’s disease (p<0,001 and p<0,008, respectively), while lactoferrin excretion significantly correlated with histological inflammation (p=0.001 and p=0.009 respectively). Recommended cut-off values need to be adjusted in the inflammatory bowel disease group. Overall sensitivity, specificity, positive predictive value, and diagnostic efficacy were 78, 83, 86, and 80% for calprotectin and 80, 85, 87, and 81% for lactoferrin, respectively.

Conclusions

Fecal calprotectin and lactoferrin appear to be equally recommendable as inflammatory disease markers in patients with lower gastrointestinal symptoms. Both tests are needed to accurately discriminate activity in inflammatory bowel disease patients.

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References

  1. Poullis A, Foster R, Mendall MA, Fagerhol MK (2003) Emerging role of calprotectin in gastroenterology. J Gastroenterol Hepatol 18(7):756–762

    Article  PubMed  CAS  Google Scholar 

  2. Kane SV, Sandborn WJ, Rufo PA, Zholudev A, Boone J, Lyerly D, Camilleri M, Hanauer SB (2003) Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. Am J Gastroenterol 98(6):1309–1314

    Article  PubMed  CAS  Google Scholar 

  3. Guerrant RL, Araujo V, Soares E, Kotloff K, Lima AA, Cooper WH, Lee AG (1992) Measurement of fecal lactoferrin as a marker of fecal leukocytes. J Clin Microbiol 30(5):1238–1242

    PubMed  CAS  Google Scholar 

  4. Martins CA, Fonteles MG, Barrett LJ, Guerrant RL (1995) Correlation of lactoferrin with neutrophilic inflammation in body fluids. Clin Diagn Lab Immunol 2(6):763–765

    PubMed  CAS  Google Scholar 

  5. Sugi K, Saitoh O, Hirata I, Katsu K (1996) Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins. Am J Gastroenterol 91(5):927–934

    PubMed  CAS  Google Scholar 

  6. Voganatsi A, Panyutich A, Miyasaki KT, Murthy RK (2001) Mechanism of extracellular release of human neutrophil calprotectin complex. J Leukoc Biol 70:130–134

    PubMed  CAS  Google Scholar 

  7. Kayazawa M, Saitoh O, Kojima K, Nakagawa K, Tanaka S, Tabata K, Matsuse R, Uchida K, Hoshimoto M, Hirata I, Katsu K (2002) Lactoferrin in whole gut lavage fluid as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins. Am J Gastroenterol 97(2):360–369

    Article  PubMed  CAS  Google Scholar 

  8. Roseth AG, Fagerhol MK, Aadland E, Schjonsby H (1992) Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand J Gastroenterol 27(9):793–798

    PubMed  CAS  Google Scholar 

  9. Fine KD, Ogunji F, George J, Niehaus MD, Guerrant RL (1998) Utility of a rapid fecal latex agglutination test detecting the neutrophil protein, lactoferrin, for diagnosing inflammatory causes of chronic diarrhea. Am J Gastroenterol 93(8):1300–1305

    Article  PubMed  CAS  Google Scholar 

  10. Gaya DR, Lyon TDB, Duncan A, Neilly JB, Han S, Howell J, Liddell C, Stanley AJ, Morris AJ, Mackenzie JF (2005) Fecal calprotectin in the assessment of Crohn’s disease activity. Q J Med 98:435–441

    CAS  Google Scholar 

  11. Summerton CB, Longlands MG, Wiener K, Shreeve DR (2002) Faecal calprotectin: a marker of inflammation throughout the intestinal tract. Eur J Gastroenterol Hepatol 14(8):841–845

    Article  PubMed  CAS  Google Scholar 

  12. Saitoh O, Kojima K, Kayazawa M, Sugi K, Tanaka S, Nakagawa K, Teranishi T, Matsuse R, Uchida K, Morikawa H, Hirata I, Katsu K (2000) Comparison of tests for fecal lactoferrin and fecal occult blood for colorectal diseases: a prospective pilot study. Intern Med 39(10):778–782

    PubMed  CAS  Google Scholar 

  13. Silberer H, Kuppers B, Mickisch O, Baniewicz W, Drescher M, Traber L, Kempf A, Schmidt-Gayk H (2005) Fecal leukocyte proteins in inflammatory bowel disease and irritable bowel syndrome. Clin Lab 51(3–4):117–126

    PubMed  CAS  Google Scholar 

  14. Langhorst J, Elsenbruch S, Mueller T, Rueffer A, Spahn G, Michalsen A, Dobos GJ (2005) Comparison of 4 neutrophil-derived proteins in feces as indicators of disease activity in ulcerative colitis. Inflamm Bowel Dis 11(12):1085–1091

    Article  PubMed  Google Scholar 

  15. Larsen A, Hovdenak N, Karlsdottir A, Wentzel-Larsen T, Dahl O, Fagerhol MK (2004) Faecal calprotectin and lactoferrin as markers of acute radiation proctitis: a pilot study of eight stool markers. Scand J Gastroenterol 30:1113–1118

    Article  CAS  Google Scholar 

  16. Schroeder KW, Tremaine WJ, Ilstrup DM (1987) Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. N Engl J Med 317:1625–1629

    Article  PubMed  CAS  Google Scholar 

  17. Floren CH, Benton C, Willen R (1987) Histological and colonoscopy assessment of disease extension in ulcerative colitis. Scand J Gastroenterol 22:459–462

    PubMed  CAS  Google Scholar 

  18. Daperno M, D’Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, Sostegni R, Rocca R, Pera A, Gevers A, Mary JY, Colombel JF, Rutgeerts P (2004) Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc 60:505–512

    Article  PubMed  Google Scholar 

  19. Fazio VW, Marchetti F, Church JM, Goldblum JR, Lavery C, Hull TL, Milsom JW, Strong SA, Oakley JR, Secic M (1996) Effect of resection margins on the recurrence of Crohn’s disease in the small bowel. Ann Surg 224:563–567

    Article  PubMed  CAS  Google Scholar 

  20. Limburg PJ, Ahlquist DA, Sandborn WJ, Mahoney DW, Devens ME, Harrington JJ, Zinsmeister AR (2000) Fecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhea referred for colonoscopy. Am J Gastroenterol 95(10):2831–2837

    Article  PubMed  CAS  Google Scholar 

  21. Carroccio A, Iacono G, Cottone M, Di Prima L, Cartabellotta F, Cavataio F, Scalici C, Montalto G, Di Fede G, Rini G, Notarbartolo A, Averna MR (2003) 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 49:861–867

    Article  PubMed  CAS  Google Scholar 

  22. Kapel N (2004) Faecal inflammatory markers in nutrition and digestive diseases in children. Arch Pediatr 11(5):403–405

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  24. Braegger CP, Nicholls S, Murch SH, Stephens S, MacDonald TT (1992) Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet 339:89–91

    Article  PubMed  CAS  Google Scholar 

  25. Tibble J, Sigthorsson G, Foster R, Sherwood R, Fagerhol M, Bjarnason I (2001) Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma. Gut 49(3):402–408

    Article  PubMed  CAS  Google Scholar 

  26. Kristjansson J, Armbruster CH, Ugstad M, Kriwanek S, Nygaard K, Ton H, Fuglerud P (2001) Fecal excretion of calprotectin in colorectal cancer: relationship to tumor characteristics. Scand J Gastroenterol 36(2):202–207

    Google Scholar 

  27. Roseth AG, Kristjansson J, Fagerhol MK, Schjonsby H, Aadland E, Nygaard K, Roald B (1993) Faecal calprotectin: a novel test for the diagnosis of colorectal cancer? Scand J Gastroenterol 28(12):1073–1076

    PubMed  CAS  Google Scholar 

  28. Poullis A, Foster R, Shetty A, Fagerhol MK, Mendal MM (2004) Bowel inflammation as measured by fecal calprotectin: a link between lifestyle factors and colorectal cancer risk. Cancer Epidemiol Biomark Prev 13:279–284

    Article  CAS  Google Scholar 

  29. Kronborg O, Ugstad M, Fuglerud P, Johne B, Hardcastle J, Scholefield JH, Vellacott K, Moshakis V, Reynolds JR (2000) Faecal calprotectin levels in a high risk population for colorectal neoplasia. Gut 46(6):795–800

    Article  PubMed  CAS  Google Scholar 

  30. Buderus S, Boone J, Lyerly D, Lentze MJ (2004) Fecal lactoferrin: a new parameter to monitor infliximab therapy. Dig Dis Sci 49(6):1036–1039

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Hanai H, Takeuchi K, Iida T, Kashiwagi N, Saniabadi AR, Matsushita I, Sato Y, Kasuga N, Nakamura T (2004) Relationship between fecal calprotectin, intestinal inflammation, and peripheral blood neutrophils in patients with active ulcerative colitis. Dig Dis Sci 49(9):1438–1443

    Article  PubMed  Google Scholar 

  33. Tibble JA, Sighthorsson G, Bridger S, Fagerhol MK, Bjarnason I (2000) Surrogate markers on intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 119:15–22

    Article  PubMed  CAS  Google Scholar 

  34. Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C, Ricchiuti A, Marchi S, Bottai M (2005) Calprotectin is a strong predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut 54:364–368

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Dr. R. D’Incà and Dr. E. Dal Pont contributed equally to this work. This is supported in part by a grant from MIUR ex 40% 2004 (2004063577_004).

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Correspondence to Renata D’Incà.

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D’Incà, 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 22, 429–437 (2007). https://doi.org/10.1007/s00384-006-0159-9

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