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Romanian Journal of Internal Medicine

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Rapid fecal calprotectin testing predicts mucosal healing better than C-reactive protein and serum tumor necrosis factor α in patients with ulcerative colitis

T. Voiosu
  • Corresponding author
  • Gastroenterology Division, “Colentina” Clinical Hospital, 19-21 Ştefan cel Mare Bvd., Bucharest, Romania
  • UMF Carol Davila School of Medicine, Eroii Sanitari Bvd., Bucharest, Romania
  • Email:
/ Andreea Benguş
  • Gastroenterology Division, “Colentina” Clinical Hospital, 19-21 Ştefan cel Mare Bvd., Bucharest, Romania
/ P. Bălănescu
  • Gastroenterology Division, “Colentina” Clinical Hospital, 19-21 Ştefan cel Mare Bvd., Bucharest, Romania
  • UMF Carol Davila School of Medicine, Eroii Sanitari Bvd., Bucharest, Romania
/ Roxana Dinu
  • Gastroenterology Division, “Colentina” Clinical Hospital, 19-21 Ştefan cel Mare Bvd., Bucharest, Romania
/ A. Voiosu
  • Gastroenterology Division, “Colentina” Clinical Hospital, 19-21 Ştefan cel Mare Bvd., Bucharest, Romania
  • UMF Carol Davila School of Medicine, Eroii Sanitari Bvd., Bucharest, Romania
/ C. Băicuş
  • Gastroenterology Division, “Colentina” Clinical Hospital, 19-21 Ştefan cel Mare Bvd., Bucharest, Romania
  • Internal Medicine Division, “Colentina” Clinical Hospital, 19-21 Ştefan cel Mare Bvd., Bucharest, Romania
/ B. Mateescu
  • Gastroenterology Division, “Colentina” Clinical Hospital, 19-21 Ştefan cel Mare Bvd., Bucharest, Romania
  • UMF Carol Davila School of Medicine, Eroii Sanitari Bvd., Bucharest, Romania
Published Online: 2015-10-14 | DOI: https://doi.org/10.1515/rjim-2015-0033

Abstract

Background and Aims. Serum and fecal biomarkers have been used as noninvasive methods for assessing disease activity in ulcerative colitis. C-reactive protein, serum tumor necrosis factor-α and fecal calprotectin are among the most promising such biomarkers. However, their role in the management of ulcerative colitis patients remains to be clarified. We aimed to evaluate the accuracy of C-reactive protein, fecal calprotectin and tumor necrosis factor-α in detecting clinical and endoscopic activity and predicting disease outcome.

Methods. A cohort of ulcerative colitis patients was prospectively evaluated for clinical and endoscopic disease activity using the Mayo score. Serum C-reactive protein and tumor necrosis factor-α levels were measured and a point-of-care method was used for determining Calprotectin levels.

Results. Fifty-three patients with ulcerative colitis were followed for a median of 12 months. Fecal calprotectin and C-reactive protein levels were significantly higher in patients with clinically active disease at baseline, but only calprotectin levels correlated with endoscopic activity. Calprotectin values over 300 μg/g had 60% sensitivity and 90% specificity for detecting active endoscopic disease and 61% sensitivity and 89% specificity for predicting mucosal healing.

Conclusion. Rapid calprotectin testing is a better predictor of mucosal healing than serum biomarkers and it could improve the management of ulcerative colitis patients by decreasing the need for invasive investigations.

Introducere. Biomarkerii serici şi fecali au un rol în evaluarea noninvazivă a activităţii bolii la pacienţii cu colită ulcerativă. Proteina C reactivă, factorul de necroză tumorală alfa şi calprotectina fecală se numără printre cei mai promiţători asemenea markeri. Cu toate acestea, rolul lor în managementul pacienţilor cu colită ulcerativă este incomplet definit.

Obiective. Ne-am propus evaluarea acurateţii diagnostice a proteinei C reactive, calprotectinei fecale şi TNFα în detecţia activităţii clinice şi endoscopice precum şi în predicţia evoluţiei pacienţilor cu colită ulcerativă.

Metode. Am evaluat prospectiv activitatea clinică şi endoscopică a bolii într-o cohortă de pacienţi cu colită ulcerativă folosind scorul Mayo. Am măsurat nivelurile serice ale PCR şi TNFα şi am cuantificat calprotectina fecală folosind o metodă rapidă semicantitativă.

Rezultate. 53 de pacienţi cu colită ulcerativă au fost urmăriţi pe o durată medie de 12 luni de zile. Calprotectina şi PCR au fost semnificativ mai mari la pacienţii cu boală clinic activă la înrolare dar numai calprotectina fecală s-a corelat cu activitatea clinică. Valori ale calprotectinei peste 300 μg/g au avut o sensibilitate de 60% şi o specificitate de 90% în detectarea activităţii endoscopice şi o sensibilitate de 61% cu o specificitate de 89% în predicţia vindecării mucosale.

Concluzii. Determinarea semicantitativă a proteinei fecale este un predictor superior al vindecării mucosale comparativ cu markerii serici şi ar putea îmbunătăţi managementul pacienţilor cu colită ulcerativă prin scăderea necesarului de examinări endoscopice invazive.

Keywords: ulcerative colitis; fecal calprotectin; C-reactive protein; mucosal healing

REFERENCES

  • 1. CIOFFI M, ROSA AD, SERAO R, et al. Laboratory markers in ulcerative colitis: Current insights and future advances. World J Gastrointest Pathophysiol. 2015; 6(1):13-22. [Crossref]

  • 2. MENDOZA JL, ABREU MT. Biological markers in inflammatory bowel disease: practical consideration for clinicians.Gastroenterol Clin Biol. 2009; 33 Suppl 3:S158. [Crossref] [Web of Science]

  • 3. HENRIKSEN M, JAHNSEN J, LYGREN I, et al. C-reactive protein a predictive factor and marker of inflammation in inflammatory bowel disease. Results from a prospective population-based study. Gut. 2008; 57(11):1518-23. [Crossref] [Web of Science]

  • 4. VAN RHEENEN PF, VAN DE VIJVER E, FIDLER V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ 2010; 341:c3369.

  • 5. 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: 803-813. [Crossref]

  • 6. TRAVIS SP, FARRANT JM, RICKETTS C, et al. Predicting outcome in severe ulcerative colitis. Gut 1996; 38:905–910. [Crossref]

  • 7. BOSCHETTI G, GARNERO P, MOUSSATA D, et al. Accuracies of Serum and Fecal S100 Proteins (Calprotectin and Calgranulin C) to Predict the Response to TNF Antagonists in Patients with Crohn's Disease. Inflamm Bowel Dis. 2015; 21(2):331-6. [Web of Science] [Crossref]

  • 8. KISS LS, SZAMOSI T, MOLNAR T, et al. Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn's disease. Aliment Pharmacol Ther. 2011; 34(8):911-22. [Crossref] [Web of Science]

  • 9. MOOIWEER E, SEVERS M, SCHIPPER ME, et al. Low fecal calprotectin predicts sustained clinical remission in inflammatory bowel disease patients: a plea for deep remission. J Crohns Colitis. 2015; 9(1):50-5. [Crossref] [Web of Science]

  • 10. 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):2218-24. [Crossref] [Web of Science]

  • 11. 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: 1851-1858. [Web of Science] [Crossref]

  • 12. 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: 1221-1229. [Web of Science] [Crossref]

  • 13. FROSLIE KF, JAHNSEN J, MOUM BA, et al. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 2007; 133:412-22.

  • 14. 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):364-8. [Crossref]

  • 15. 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):1022-9. [Web of Science] [Crossref]

  • 16. CESARO A, ANCERIZ N, PLANTE A, et al. An inflammation loop orchestrated by S100A9 and calprotectin is critical for the development of arthritis. PLoS One. 2012; 7(9): e45478. [Web of Science] [Crossref]

  • 17. FEGHALI CA, WRIGHT TM. Cytokines in acute and chronic inflammation. Front Biosci. 1997 1; (2):d12-26.

  • 18. VERMEIRE S, VAN ASSCHE G, RUTGEERTS P.C-reactive protein as a marker for inflammatory bowel disease. Inflamm Bowel Dis. 2004; 10(5):661-5. [Crossref] [Web of Science]

  • 19. VATAY A, BENE L, KOVÁCS A, et al. Relationship between the tumor necrosis factor alpha polymorphism and the serum C-reactive protein levels in inflammatory bowel disease. Immunogenetics. 2003; 55(4):247-52. [Crossref]

  • 20. COLOMBEL JF, RUTGEERTS P, REINISCH W, et al. Early mucosal healing with infliximab is associated with improved longterm clinical outcomes in ulcerative colitis. Gastroenterology 2011; 141:1194-201.

  • 21. FENG JS, YANG Z, ZHU YZ, et al. Serum IL-17 and IL-6 increased accompany with TGF-β and IL-13 respectively in ulcerative colitis patients. Int J Clin Exp Med. 2014; 7(12):5498-504.

  • 22. OWCZAREK D, CIBOR D, GŁOWACKI MK, et al. TNF-α and soluble forms of TNF receptors 1 and 2 in the serum of patients with Crohn's disease and ulcerative colitis. Pol Arch Med Wewn. 2012; 122(12):616-23.

  • 23. SCHROEDER KW, TREMAINE WJ, ILSTRUP DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 1987; 317: 1625–9.

  • 24. VAN ASSCHE G, DIGNASS A, PANES J, et al. European Crohn's and Colitis Organisation (ECCO). 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 [Web of Science] [Crossref]

  • 25. DIGNASS A, ELIAKIM R, MAGRO F, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J Crohns Colitis. 2012; 6(10):965-90. [Web of Science]

  • 26. SCHOEPFER AM, VAVRICKA S, ZAHND-STRAUMANN N, et al. Monitoring infammatory bowel disease activity: clinical activity is judged to be more relevant than endoscopic severity or biomarkers. J Crohns Colitis 2012; 6:412-418. [Web of Science] [Crossref]

  • 27. RODA G, CAPONI A, BENEVENTO M, et al. New proteomic approaches for biomarker discovery in inflammatory bowel disease. Inflamm Bowel Dis. 2010; 16(7):1239-46. [Web of Science] [Crossref]

  • 28. FAUBION WA JR1, FLETCHER JG, O'BYRNE S, et al. EMerging BiomARKers in Inflammatory Bowel Disease (EMBARK) study identifies fecal calprotectin, serumMMP9, and serum IL-22 as a novel combination of biomarkers for Crohn's disease activity: role of cross-sectional imaging. Am J Gastroenterol. 2013; 108(12):1891-900.

  • 29. 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. [Web of Science] [Crossref]

  • 30. SCHMIDT C, GIESE T, HERMANN E, et al. Predictive value of mucosal TNF-alpha transcripts in steroid-refractory Crohn's disease patients receiving intensive immunosuppressive therapy. Inflamm Bowel Dis. 2007;13(1):65-70. [Crossref] [Web of Science]

  • 31. DIONNE S, HISCOTT J, D'AGATA I et al. Quantitative PCR analysis of TNF-alpha and IL-1 beta mRNA levels in pediatric IBD mucosal biopsies. Dig Dis Sci. 1997; 42(7):1557-66. [Crossref]

  • 32. MARTÍNEZ-BORRA J, LÓPEZ-LARREA C, GONZÁLEZ S, et al. High serum tumor necrosis factor-alpha levels are associated with lack of response to infliximab in fistulizing Crohn's disease. Am J Gastroenterol. 2002; 97(9):2350-6.

  • 33. SYDORA MJ, SYDORA BC, FEDORAK RN. Validation of a point-of-care desk top device to quantitate fecal calprotectin and distinguish inflammatory bowel disease from irritable bowel syndrome. J Crohns Colitis. 2012; 6(2):207-14 [Web of Science] [Crossref]

  • 34. VOIOSU T, BENGUŞ A, DINU R, et al. Rapid fecal calprotectin level assessment and the SIBDQ score can accurately detect active mucosal inflammation in IBD patients in clinical remission: a prospective study. J Gastrointestin Liver Dis. 2014; 23(3):273-8. [Web of Science]

  • 35. 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: 162-169. [Web of Science] [Crossref]

  • 36. YOON JY, PARK SJ, HONG SP et al. Correlations of C-reactive protein levels and erythrocyte sedimentation rates with endoscopic activity indices in patients with ulcerative colitis. Dig Dis Sci. 2014; 59(4):829-37. [Crossref] [Web of Science]

  • 37. 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):332-41. [Crossref] [Web of Science]

  • 38. LEWIS JD. The utility of biomarkers in the diagnosis and therapy of inflammatory bowel disease. Gastroenterology. 2011; 140(6):1817-1826. [Crossref]

  • 39. MARTÍNEZ-BORRA J, LÓPEZ-LARREA C, GONZÁLEZ S, et al. High serum tumor necrosis factorα are associated with lack of response to infliximab in fistulizing Crohn’s disease. Am J Gastroenterol 2002; 97(9):2350-6.

  • 40. OLSEN T, GOLL R, CUI G et al. Tissue levels of tumor necrosis factor-alpha correlates with grade of inflammation in untreated ulcerative colitis. Scand J Gastroenterol. 2007; 42(11):1312-20. [Web of Science] [Crossref]

  • 41. KOMATSU M, KOBAYASHI D, SAITO K. Tumor necrosis factor-alpha in serum of patients with inflammatory bowel disease as measured by a highly sensitive immuno-PCR. Clin Chem. 2001; 47(7):1297-301.

  • 42. RODRÍGUEZ-PERÁLVAREZ ML, GARCÍA-SÁNCHEZ V, VILLAR-PASTOR CM, et al. Role of serum cytokine profile in ulcerative colitis assessment. Inflamm Bowel Dis. 2012; 18(10):1864-71. [Web of Science] [Crossref]

  • 43. 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):2111-7. [Web of Science] [Crossref]

  • 44. 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):144-52. [Crossref]

About the article

Received: 2015-05-31

Published Online: 2015-10-14

Published in Print: 2015-09-01


Citation Information: Romanian Journal Of Internal Medicine, ISSN (Online) 1220-4749, DOI: https://doi.org/10.1515/rjim-2015-0033. Export Citation

© 2015 T. Voiosu et al., published by De Gruyter Open. This chapter is distributed under the terms of the Creative Commons Attribution 4.0 Public License. (CC BY 4.0)

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