Skip to main content
Log in

Fecal calprotectin and lactoferrin as predictors of relapse in patients with quiescent ulcerative colitis during maintenance therapy

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

This prospective study was to evaluate the significance of fecal calprotectin and lactoferrin for the prediction of ulcerative colitis (UC) relapse.

Methods

Eighty UC patients in remission for ≥3 months on mesalamine as maintenance therapy were included. At entry, stool samples were collected for the measurement of calprotectin and lactoferrin. All patients were followed up for the following 12 months. To identify predictive factors for relapse, time-dependent analyses using the Kaplan-Meier graphs and Cox's proportional hazard model were applied.

Results

During the 12 months, 21 patients relapsed. Mean calprotectin and lactoferrin levels were significantly higher in patients with relapse than those in remission (calprotectin—173.7 vs 135.5 μg/g, P = 0.02; lactoferrin—165.1 vs 130.7 μg/g, P = 0.03). A cutoff value of 170 μg/g for calprotectin had a sensitivity of 76 % and a specificity of 76 % to predict relapse, while a cutoff value of 140 μg/g for lactoferrin had a sensitivity of 67 % and a specificity of 68 %. In a multivariate analysis, calprotectin (≥170 μg/g) was a predictor of relapse (hazard ratio, 7.23; P = 0.002). None of the following parameters were significantly associated with relapse: age, gender, duration of UC, number of UC episode, severity of the previous episode, extent of UC, extraintestinal manifestation, and lactoferrin level.

Conclusions

Fecal calprotectin showed a higher sensitivity and specificity than fecal lactoferrin for predicting UC relapse. Fecal calprotectin level appeared to be a significant predictor of relapse in patients with quiescent UC on mesalamine as maintenance therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Langholz E, Munkholm P, Davidsen M, Binder V (1994) Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology 107:3–11

    PubMed  CAS  Google Scholar 

  2. Leo S, Leandro G, Di Matteo G, Caruso ML, Lorusso D (1989) Ulcerative colitis in remission: is it possible to predict the risk of relapse? Digestion 44:217–221

    Article  PubMed  CAS  Google Scholar 

  3. Riley SA, Mani V, Goodman MJ, Lucas S (1990) Why do patients with ulcerative colitis relapse? Gut 31:179–183

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Levenstein S, Prantera C, Varvo V, Scribano ML, Andreoli A, Luzi C et al (2000) Stress and exacerbation in ulcerative colitis: a prospective study of patients enrolled in remission. Am J Gastroenterol 95:1213–1220

    Article  PubMed  CAS  Google Scholar 

  5. Bitton A, Peppercorn MA, Antonioli DA, Niles JL, Shah S, Bousvaros A et al (2001) Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology 120:13–20

    Article  PubMed  CAS  Google Scholar 

  6. Bischoff SC, Grabowsky J, Manns MP (1997) Quantification of inflammatory mediators in stool samples of patients with inflammatory bowel disorders and controls. Dig Dis Sci 42:394–403

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. 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 

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

    Article  PubMed  CAS  Google Scholar 

  10. Johne B, Fagerhol MK, Lyberg T, Prydz H, Brandtzaeg P, Naess-Andresen CF et al (1997) Functional and clinical aspects of the myelomonocytic protein calprotectin. J Clin Pathol Mol Pathol 50:113–123

    Article  CAS  Google Scholar 

  11. Baveye S, Elass E, Mazurier J, Spik G, Legrand D (1999) Lactoferrin: a multifunctional glycoprotein involved in the modulation of the inflammatory process. Clin Chem Lab Med 37:281–286

    Article  PubMed  CAS  Google Scholar 

  12. Baynes RD, Bezwoda WR (1994) Lactoferrin and the inflammatory response. Adv Exp Med Biol 357:133–141

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. 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 91:927–934

    PubMed  CAS  Google Scholar 

  15. Jones J, Loftus EV Jr, Panaccione R, Chen LS, Peterson S, McConnell J et al (2008) Relationships between disease activity and serum and fecal biomarkers in patients with Crohn's disease. Clin Gastroenterol Hepatol 6:1218–1224

    Article  PubMed  Google Scholar 

  16. Sipponen T, Kärkkäinen P, Savilahti E, Kolho KL, Nuutinen H, Turunen U et al (2008) Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn's disease and histological findings. Aliment Pharmacol Ther 28:1221–1229

    Article  PubMed  CAS  Google Scholar 

  17. Sipponen T, Björkesten CG, Färkkilä M, Nuutinen H, Savilahti E, Kolho KL (2010) Faecal calprotectin and lactoferrin are reliable surrogate markers of endoscopic response during Crohn's disease treatment. Scand J Gastroenterol 45:325–331

    Article  PubMed  CAS  Google Scholar 

  18. D'Haens G, Ferrante M, Vermeire S, Baert F, Noman M, Moortgat L et al (2012) Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 18:2218–2224

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C et al (2005) Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease. Gut 54:364–368

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. D'Inca R, Dal Pont E, Di Leo V, Benazzato L, Martinato M, Lamboglia F et al (2008) Can calprotectin predict relapse risk in inflammatory bowel disease? Am J Gastroenterol 103:2007–2014

    Article  PubMed  CAS  Google Scholar 

  22. Walkiewicz D, Werlin SL, Fish D, Scanlon M, Hanaway P, Kugathasan S (2008) Fecal calprotectin is useful in predicting disease relapse in pediatric inflammatory bowel disease. Inflamm Bowel Dis 14:669–673

    Article  PubMed  Google Scholar 

  23. Gisbert JP, Bermejo F, Perez-Calle JL, Taxonera C, Vera I, McNicholl AG et al (2009) Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse. Inflamm Bowel Dis 15:1190–1198

    Article  PubMed  Google Scholar 

  24. García-Sánchez V, Iglesias-Flores E, González R, Gisbert JP, Gallardo-Valverde JM, González-Galilea A et al (2010) Does fecal calprotectin predict relapse in patients with Crohn's disease and ulcerative colitis? J Crohns Colitis 4:144–152

    Article  PubMed  Google Scholar 

  25. Sutherland LR, Martin F, Greer S, Robinson M, Greenberger N, Saibil F et al (1987) 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. Gastroenterology 92:1984–1988

    Google Scholar 

  26. Brannigan AE, O'Connell PR, Hurley H, O'Neill A, Brady HR, Fitzpatrick JM et al (2000) Neutrophil apoptosis is delayed in patients with inflammatory bowel disease. Shock 13:361–366

    Article  PubMed  CAS  Google Scholar 

  27. McCarthy DA, Rampton DS, Liu YC (1991) Peripheral blood neutrophils in inflammatory bowel disease: morphological evidence of in vivo activation in active disease. Clin Exp Immunol 86:489–493

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Competing interests

None.

External funding

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takayuki Yamamoto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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 Colorectal Dis 29, 485–491 (2014). https://doi.org/10.1007/s00384-013-1817-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-013-1817-3

Keywords

Navigation