Fecal sST2 correlates with the disease severity of ulcerative colitis

  • Marina Jovanovic University of Kragujevac, Faculty of Medical Sciences, Department of Internal Medicine, Kragujevac, Serbia
  • Nevena Gajovic University of Kragujevac, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, Kragujevac, Serbia
  • Milena Jurisevic University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacy, Kragujevac, Serbia
  • Bojana Simovic Markovic University of Kragujevac, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, Kragujevac, Serbia
  • Veljko Maric University of East Sarajevo, Faculty of Medicine, Department of Surgery, Foča, Bosnia and Herzegovina;
  • Milan Jovanovic Military Medical Academy, Department of Abdominal Surgery, Belgrade, Serbia; University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
  • Nebojsa Arsenijevic University of Kragujevac, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, Kragujevac, Serbia
  • Natasa Zdravkovic University of Kragujevac, Faculty of Medical Sciences, Department of Internal Medicine, Kragujevac, Serbia
Keywords: colitis, ulcerative, biomarkers, disease progression, feces, tumor necrosis factor-alpha, interleukin-10, interleukin-17, il1rl1 protein, human

Abstract


Abstract

 

Background/Aim. Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease affecting the distal colon and rectum with complex pathogenesis and diagnosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine the fecal values of TNF-α, IL-17, IL-10 and soluble protein ST2 (sST2) in the patients with UC and their relationship with clinicopathological aspects. Methods. The samples of stool of 80 patients with UC were analyzed. Concentrations of TNF-α, IL-17, IL-10 and sST2 were measured by ELISA. Results. Concentrations of TNF-α, IL-17 and sST2 were significantly increased in the feces of patients with the higher endoscopic, clinical and total Mayo score, as well as in the patients with an intense crypt destruction, erosion of the mucous membranes, architectural changes, neutrophil infiltration and eosinophil infiltration. The local value of anti-inflammatory cytokine IL-10 in liquid fraction of feces was increased in the patients with an advanced endoscopic stage of UC. The moderate positive correlation between the fecal sST2/IL-17 and the clinical and histological parameters of disease severity and also the strong correlation between sST2 and IL-17 was also observed in the feces of patients with UC. The analysis of receiver operating characteristic (ROC) curves showed that the optimal cut-off value for sST2 of 624.0 pg/g allows the discrimination of clinical stages of UC. Conclusion. The increased fecal value of sST2 in the UC patients with a higher endoscopic, clinical and histological stage of disease may be considered as a sign of the disease severity. The fecal values of sST2 can be used as a valuable marker for UC severity.

References

REFERENCES

Matkowskyj KA, Chen ZE, Rao MS, Yang G. Dysplastic lesions in inflammatory bowel disease: molecular pathogenesis to morphology. Arch Pathol Lab Med 2013; 137(3): 338–50.

Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347(6): 417–29.

Raza A, Yousaf W, Giannella R, Shata MT. Th17 cells: interac-tions with predisposing factors in the immunopathogenesis of inflammatory bowel disease. Exp Rev Clin Immunol 2012; 8(2): 161–8.

Xavier RJ, Podolsky DK. Unravelling the pathogenesis of in-flammatory bowel disease. Nature 2007; 448(7152): 427–34.

Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol 2014; 14(5): 329–42.

Sandborn WJ, Hanauer SB. Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharma-cology, clinical results, and safety. Inflamm Bowel Dis 1999; 5(2): 1119–33.

Ito R, Shin-Ya M, Kishida T, Urano A, Takada R, Sakagami J, et al. Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice. Clin Exp Immunol 2006; 146(2): 330–8.

Műzes G, Molnґar B, Tulassay Z, Sipos F. Changes of the cyto-kine profile in inflammatory bowel diseases. World J Ga-stroenterol 2012; 18(41): 5848–61.

Jovanovic M, Zdravkovic N, Jovanovic I, Radosavljevic G, Gajovic N, Zdravkovic N, et al. TGF-β as a marker of ulcerative colitis and disease severity. Ser J Exp Clin Res 2017; DOI: 10.1515/sjecr-2017-0019.

Fuss IJ, Heller F, Boirivant M, Leon F, Yoshida M, Fichtner-Feigl S, et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative coli-tis. J Clin Invest 2004; 113(10): 1490–7. 1

Mańkowska-Wierzbicka D, Swora-Cwynar E, Poniedziałek B, Adamski Z, Dobrowolska A, Karczewski J. Usefulness of selected laboratory markers in ulcerative colitis. Eur Cytokine Netw 2015; 26(2): 26–37.

Schoepfer AM, Vavricka S, Zahnd-Straumann N, Straumann A, Beglinger C. Monitoring inflammatory bowel disease activity: Clinical activity is judged to be more relevant than endoscopic severity or biomarkers. J Crohns Colitis 2012; 6(4): 412–8.

Cooney RM, Warren BF, Altman DG, Abreu MT, Travis SP. Outcome measurement in clinical trials for ulcerative colitis: towards standardisation. Trials 2007; 8: 17.

Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006; 55(6): 749–53.

Hiraoka S, Inokuchi T, Nakarai A, Takashima S, Takei D, Sugihara Y, et al. Fecal immunochemical test and fecal calprotectin results show different profiles in disease monitoring for ulcerative colitis. Gut Liver 2018; 12(2): 142–8.

Dignass A, Eliakim R, Magro F, Maaser C, Chowers Y, Geboes K, 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.

Gomollón F, García-López S, Sicilia B, Gisbert JP, Hinojosa J. Grupo Espa˜nol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa . Therapeutic guidelines on ulcerative colitis: A GRADE methodology based effort of GETECCU. Gastroen-terol Hepatol 2013; 36(2): 104–14.

Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis. N Eng J Med 2005; 353(23): 2462–76.

D'Haens G, Sandborn WJ, Feagan BG, Geboes K, Hanauer SB, Ir-vine EJ, et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology 2007; 132(2): 763–86.

Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Löfberg R. A re-producible grading scale for histological assessment of in-flammation in ulcerative colitis. Gut 2000; 47(3): 404–9.

Heilmann RM, Cranford SM, Ambrus A, Grützner N, Schellenberg S, Ruaux CG, et al. Validation of an enzyme-linked immuno-sorbent assay (ELISA) for the measurement of canine S100A12. Vet Clin Pathol 2016; 45(1): 135–47.

Prakash N, Stumbles P, Mansfield C. Initial validation of cytokine measurement by ELISA in canine feces. Open J Vet Med 2013; 3(6): 282–8.

Langhorst J, Elsenbruch S, Kölzer J, Rueffer A, Michalsen A, Dobos GJ. Noninvasive Markers in the Assessment of Intestinal In-flammation in Inflammatory Bowel Diseases: Performance of Fecal Lactoferrin, Calprotectin, and PMN-Elastase, CRP, and Clinical Indices. Am J Gastroenterol 2008; 103(1): 162–9.

Vermeire S, van Assche G, Rutgeerts P. Laboratory markers in IBD: Useful, magic, or unnecessary toys? Gut 2006; 55(3): 426–31.

Kopylov U, Rosenfeld G, Bressler B, Seidman E. clinical utility of fecal biomarkers for the diagnosis and management of in-flammatory bowel disease. Inflamm Bowel Dis 2014; 20(4): 742–56.

Lewis JD. The utility of biomarkers in the diagnosis and thera-py of inflammatory bowel disease. Gastroenterology 2011; 140(6): 1817–26.e2.

Boon GJ, Day AS, Mulder CJ, Gearry RB. Are faecal markers good indicators of mucosal healing in inflammatory bowel dis-ease? World J Gastroenterol 2015; 21(40): 11469–80.

Murch SH, Braegger CP, Walker Smith JA, MacDonald TT. Loca-tion of tumour necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease. Gut 1993; 34(12): 1705–9.

Zdravkovic ND, Jovanovic IP, Radosavljevic GD, Arsenijevic AN, Zdravkovic ND, Mitrovic SL, et al. Potential dual immunomodulatory role of VEGF in ulcerative colitis and colorectal carcinoma. Int J Med Sci 2014; 11(9): 936–47.

Willrich MA, Murray DL, Snyder MR. Tumor necrosis factor inhibitors: clinical utility in autoimmune diseases. Trans Res 2015; 165(2): 270–82.

Colombel J, Sandborn WJ , Ghosh S, Wolf Douglas C , Panaccione R, Feagan B, et al. Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: data from ULTRA 1, 2 and 3. Am J Gastroenterol 2014; 109(11): 1771–80.

Bradley JR. TNF-mediated inflammatory disease. Journal of Pathology 2008; 214(2): 149–60.

Begue B, Wajant H, Bambou J, Dubuquoy L, Siegmund D, Beaulieu J, et al. Implication of TNF-related apoptosis-inducing ligand in inflammatory intestinal epithelial lesions. Gastroenterology 2006; 130(7): 1962–74.

Braegger CP, Nicholls S, Murch SH, MacDonald TT, Stephens S. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet 1992; 339(8785): 89–91.

Maeda M, Watanabe N, Neda H, Yamauchi N, Okamoto T, Sasaki H, et al. Serum tumor necrosis factor activity in inflammatory bowel disease. Immunopharmacol Immunotox 1992; 14(3): 451–61.

Reimund JM, Wittersheim C, Dumont S, Muller CD, Baumann R, Poindron P, et al. Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn's disease. J Clin Immunol 1996; 16(3): 144–50.

Abraham C, Cho J. Interleukin-23/Th17 pathways and inflam-matory bowel disease. Inflamm Bowel Dis 2009; 15(7): 1090–100.

Öhman L, Dahlén R, Isaksson S, Sjöling Å, Wick M, Sjövall H, et al. Serum IL-17A in newly diagnosed treatment-naive patients Laboratory markers in ulcerative colitis 35 with ulcerative colitis reflects clinical disease severity and predicts the course of disease. Inflamm Bowel Dis 2013; 19(11): 2433–9.

Shen W, Durum SK. Synergy of IL-23 and Th17 Cytokines: new light on inflammatory bowel disease. Neurochem Res 2010; 35(6): 940–6.

Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 2003; 52(1): 65–70.

Karczewski J, Mazur M, Karczewski M. Dual role of Th17 cells in Crohn’s disease. Central Eur J Immunol 2012; 37: 286–9

O'Connor W Jr, Kamanaka M, Booth CJ, Town T, Nakae S, Iwaku-ra Y, et al. A protective function for interleukin 17A in T cell–mediated intestinal inflammation. Nat Immunol 2009; 10(6): 603–9.

Kobayashi T, Okamoto S, Hisamatsu T, Kamada N, Chinen H, Saito R, et al. IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn's disease. Gut 2008; 57(12): 1682–9.

Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cyto-kine production by Th1 clones. J Exp Med 1989; 170(6): 2081–95.

Paul G, Khare V, Gasche C. Inflamed gut mucosa: downstream of interleukin-10. Eur J Clin Invest 2011; 42(1): 95–109.

Pavlović S, Zdravković N, Radosavljević G, Arsenijević N, Lukić M, Jovanović I. Interleukin-33/ST2: A new signaling pathway in immunity and immunopathology. Vojnosanit Pregl 2012; 69(1): 69–77.

Kuroiwa K, Arai T, Okazaki H, Minota S, Tominaga S. Identifica-tion of Human ST2 Protein in the Sera of Patients with Au-toimmune Diseases. Biochem Biophys Res Commun 2001; 284(5): 1104–8.

Mok MY, Huang FP, Ip WK, Lo Y, Wong FY, Chan EY, et al. Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus. Rheumatology (Oxford) 2010; 49(3): 520–7.

Díaz Jiménez D, Núñez LE, Beltrán CJ, Candia E, Suazo C, Alvarez Lobos M, et al. Soluble ST2: A new and promising activity marker in ulcerative colitis. World J Gastroenterol 2011; 17(17): 2181–90.

Lv R, Zhao J, Lei M, Xiao D, Yu Y, Xie J. IL-33 Attenuates sepsis by inhibiting il-17 receptor signaling through upregulation of socs3. Cell Physiol Biochem 2017; 42(5): 1961–72.

Jiang H, Milovanović M, Allan D, Niedbala W, Besnard A, Fukada SY, et al. IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macro-phages. Eur J Immunol 2012; 42(7): 1804–14.

Published
2021/05/26
Section
Original Paper