Fecal calgranulin C in patients with inflammatory bowel disease

Czech version

Authors: K. Malíčková ¹; M. Bortlík ^2,3; D. Ďuricová ^2,4; M. Lukáš ^2,3; Luděk Hrdlička ²; N. Machková ²; M. Lukáš ^1,2
Authors‘ workplace: Ústav lékařské biochemie a laboratorní diagnostiky 1. LF UK a VFN, Praha ¹; Klinické a výzkumné centrum pro střevní záněty ISCARE I. V. F. a. s. a 1. LF UK, Praha ²; Interní klinika 1. LF UK a ÚVN, Praha ³; Farmakologický ústav, 1. LF UK, Praha ⁴
Published in: Gastroent Hepatol 2014; 68(1): 10-13
Category: IDB: Original Article

Overview

The aims of the study are the analysis of fecal calgranulin C levels in patients with bowel inflammation; comparison with the fecal calprotectin test; calculation of sensitivity and specificity for the diagnosis of inflammatory bowel disease (IBD); determination of the variability parameters of enzyme-linked immunosorbent assay (ELISA) for calgranulin C detection.

Materials and Methods:
Fifty fecal samples from patients with Crohn’s disease (n = 21), ulcerative colitis (n = 19) and unspecified bowel disorders (n = 10) were analysed. The fecal levels of calprotectin (MRP8/14) and calgranulin C (MRP6) were compared in the eluates. Statistical data analysis consisted of a quantitative and qualitative results comparison, a measurement of variability parameters and diagnostic performance of both tests. In calgranulin C the reference range of normal values was estimated.

Results:
A significant positive correlation between fecal calprotectin concentrations and calgranulin C was found (r = 0.829, p <0.001). During the qualitative analysis of the results, a method consensus was achieved in 90% of cases. Diagnostic sensitivity of fecal calgranulin C for diagnosis of IBD was 75%, and specificity reached 88%. Parameters of variability for fecal calgranulin C ELISA were in accordance with ISO15189 requirements.

Conclusion:
Calgranulin C is a new biomarker of intestinal inflammation. It shows significant correlation with fecal calprotectin but its level should be increased primarily in the course of a neutrophil-mediated inflammation.

Keywords:
calgranulin C – calprotectin – S100 proteins – inflammatory bowel 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.

Submitted:
16. 9. 2013

Accepted:
9. 12. 2013

Sources

1. Kamenář D, Špičák J. Kalprotektin ve stolici. Prakt Lék 2011; 91(11): 665–669.

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

3. Adamcová M, Bajer M, Bajerová K et al. Doporučený postup pro diagnostiku IBD. Čes-slov Pediat 2012; 67 (Suppl 2): 6–12.

4. Canani RB, Terrin G, Rapacciuolo L et al. Faecal calprotectin as reliable non-invasive marker to assess the severity of mucosal inflammation in children with inflammatory bowel disease. Dig Liver Dis 2008; 40(7): 547–553. doi: 10.1016/j.dld.2008.01.017.

5. 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.

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

7. Schoepfer AM, Trummler M, Seeholzer P et 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.

8. Amati L, Passeri ME, Selicato F et al. New insights into the biological and clinical significance of fecal calprotectin in inflammatory bowel disease. Immunopharmacol Immunotoxicol 2006; 28(4): 665–681.

9. 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.

10. Drastich P, Špičák J. Komentáře k některým abstraktům posterů prezentovaných na UEGW 2009 v Londýně na téma Idiopatické střevní záněty. Čes a Slov Gastroent Hepatol 2010; 64(1): 34–39.

11. Budczies J, Klauschen F, Sinn BV et al. Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS One 2012; 7(12): e51862. doi: 10.1371/journal.pone.0051862.

12. Malíčková K, Janatková I, Bortlík M et al. Stanovení koncentrace kalprotektinu ve stolici u nemocných s idiopatickými střevními záněty – srovnání dvou komerčních testů. Epidemiol Mikrobiol Imunol 2008; 57(4): 147–153.

13. ISO 15189:2012 Medical laboratories – Requirements for quality and competence. Available from: www.iso.org.

14. Friedecký B, Šprongl L, Kratochvíla J et al. Doporučení k provádění validace a verifikace analytických metod v klinických laboratořích. Klin Biochem Metab 2011; 19(40/1): 36–44.

15. Pietzsch J, Hoppmann S. Human S100A12: a novel key player in inflammation? Amino Acids 2009; 36(3): 381–389. doi: 10.1007/s00726-008-0097-7.

16. Guignard F, Mauel J, Markert M. Identification and characterization of a novel human neutrophil protein related to the S100 family. Biochem J 1995; 309(2): 395–401.

17. Yilmaz Y, Yonal O, Eren F et al. Serum levels of soluble receptor for advanced glycation endproducts (sRAGE) are higher in ulcerative colitis and correlate with disease activity. J Crohns Colitis 2011; 5(5): 402–406. doi: 10.1016/j.crohns.2011.03.011.

18. Liu K, Pichichero ME. Clinical significance of serum S100A12 in acute otitis media in young children. Pediatr Infect Dis J 2012; 31(3): e56–e58. doi: 10.1097/INF.0b013e31824672cb.

19. Han EC, Cho SB, Ahn KJ et al. Expression of pro-inflammatory protein S100A12 (EN-RAGE) in Behçet's disease and its association with disease activity: a pilot study. Ann Dermatol 2011; 23(3): 313–320. doi: 10.5021/ad.2011.23.3.313.

20. Kallinich T, Wittkowski H, Keitzer R et al. Neutrophil-derived S100A12 as novel biomarker of inflammation in familial Mediterranean fever. Ann Rheum Dis 2010; 69(4): 677–682. doi: 10.1136/ard.2009.114363.

21. Foell D, Ichida F, Vogl T et al. S100A12 (EN-RAGE) in monitoring Kawasaki di-sease. Lancet 2003; 361(9365): 1270–1272.

22. Foell D, Wittkowski H, Ren Z et al. Phagocyte-specific S100 proteins are released from affected mucosa and promote immune responses during inflammatory bowel disease. J Pathol 2008; 216(2): 183–192. doi: 10.1002/path.2394.

23. Lukáš M. Mezinárodní konsenzus ke sledování aktivity nemoci u pacientů s Crohnovou chorobou. Výsledky projektu IBD AHEAD 2011. Gastroent Hepatol 2012; 66(2): 136–141.