Inanc KARAKOYUN, Ferruh Kemal ISMAN, Banu Isbilen BASOK, Fatma Demet ARSLAN, Bulent CALİK, Nevin Genc KAHRAMAN, Gokhan AKBULUT, Celal ULASOGLU

Serum Fetuin A and Secreted Phosphoprotein 24 as Diagnostic Markers in Inflammatory Bowel Disease

Purpose: A completely satisfactory biomarker has yet to be identified for the diagnosis and characterization of inflammatory bowel disease IBD . This study evaluated the utility of fetuin A and secreted phosphoprotein 24 kDa Spp24 as novel biomarkers in IBD. Methods: Ninety IBD patients, 54 with ulcerative colitis UC and 36 with Crohn’s disease CD , and 41 healthy controls HC were included. Serum fetuin A, Spp24, TNF-α, and IFN-γ levels were analyzed by ELISA. Serum C-reactive protein CRP levels were determined turbidimetrically by an automated procedure. Results: There were no significant differences in serum Spp24 levels among the UC 17.15 pg/mL, mean , CD 18.88 pg/mL , and HC 14.77 pg/mL groups P>0.05 . Median fetuin A levels were significantly lower in the UC 249 mg/L and CD 254 mg/L groups compared to HC 352 mg/L UC vs. HC P

Keywords:

Fetuin A, inflammatory bowel disease, secreted phosphoprotein 24,

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1. de Souza HSP, Fiocchi C. Immunopathogenesis of IBD. current state of the art. Nat Rev Gastroenterol Hepatol 2016;13:13–27. [CrossRef]
2. Hagel AF, de Rossi T, Konturek PC, et al. Plasma histamine and tumour necrosis factor-alpha levels in crohn’s disease and ulcerative colitis at various stages of disease. J Physiol Pharmacol 2015;66:549–556. http:// www.jpp.krakow.pl/journal/archive/08_15/pdf/549_08_15_article.pdf
3. Iskandar HN, Ciorba MA. Biomarkers in inflammatory bowel disease: current practices and recent advances. Transl Res 2012;159:313–325. [CrossRef]
4. Wasinger VC, Yau Y, Duo X, et al. Low mass blood peptides discriminative of inflammatory bowel disease (IBD) severity: A quantitative proteomic perspective. Mol Cell Proteomics 2016;15:256–265. [CrossRef]
5. Liu Y, Chen X, Xu Q, et al. SPP2 mutations cause autosomal dominant retinitis pigmentosa. Sci Rep 2015;5:14867. [CrossRef]
6. Gurbuz C, Polat H, Yildirim A, Canat L, Bayram G, Çaskurlu T. The role of alpha2-heremans schmid glycoprotein (Fetuin-A) in the etiology of urolithiasis. Curr Urol 2010;4:10–14. [CrossRef]
7. Ombrellino M, Wang H, Yang H, et al. Fetuin, a negative acute phase protein, attenuates TNF synthesis and the innate inflammatory response to carrageenan. Shock 2001;15:181–185. [CrossRef]
8. Bonyadi M, Abdolmohammadi R, Jahanafrooz Z, Somy MH, Khoshbaten M. TNF-alpha gene polymorphisms in Iranian Azari Turkish patients with inflammatory bowel diseases. Saudi J Gastroenterol 2014;20:108–112. [CrossRef]
9. Műzes G, Molnár B, Tulassay Z, Sipos F. Changes of the cytokine profile in inflammatory bowel diseases. World J Gastroenterol 2012;18:5848–5861. [CrossRef]
10. Manolakis AC, Christodoulidis G, Kapsoritakis AN, et al. α2- Heremans-schmid glycoprotein (fetuin A) downregulation and its utility in inflammatory bowel disease. World J Gastroenterol 2017;23:437–446. [CrossRef]
11. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a crohn’s disease activity index. National cooperative crohn’s disease study. Gastroenterology 1976;70:439–444. [CrossRef]
12. Sandborn WJ, Feagan BG, Hanauer SB, et al. A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with crohn’s disease. Gastroenterology 2002;122:512–530. [CrossRef]
13. Gasche C, Scholmerich J, Brynskov J, et al. A simple classification of crohn’s disease: report of the working party for the world congresses of gastroenterology, Vienna 1998. Inflamm Bowel Dis 2000;6:8–15. [CrossRef]
14. Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005;19:5A–36A. [CrossRef]
15. Chang S, Malter L, Hudesman D. Disease monitoring in inflammatory bowel disease. World J Gastroenterol 2015;21:11246–11259. [CrossRef]
16. Hosmer DW, Lemeshow SL. Applied Logistic Regression, 2nd ed. Wiley: New York; 2000. http://resource.heartonline. cn/20150528/1_3kOQSTg.pdf
17. Van Assche G, Dignass A, Panes J, et al; European Crohn’s and Colitis Organization (ECCO). The second European evidencebased consensus on the diagnosis and management of crohn’s disease: Definitions and diagnosis. J Crohns Colitis 2010;4:7–27. [CrossRef]
18. Dignass A, Eliakim R, Magro F, et al. Second European evidencebased consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J Crohns Colitis 2012;6:965– 990. [CrossRef]
19. Pepys MB and Hirschfield GM. C-reactive protein: A critical update. J Clin Invest 2003;111:1805–1812. [CrossRef]
20. S Vermeire, G Van Assche, P Rutgeerts. Laboratory markers in IBD. useful, magic, or unnecessary toys? Gut 2006;55:426–431. [CrossRef]
21. Lewis JD. C-reactive protein: anti-placebo or predictor of response. Gastroenterology 2005;129:1114–1116. [CrossRef]
22. Hu B, Coulson L, Moyer B, Price PA. Isolation and molecular cloning of a novel bone phosphoprotein related in sequence to the cystatin family of thiol protease inhibitors. J Biol Chem 1995;270:431–436. [CrossRef]
23. Jersmann HP, Dransfield I, Hart SP. Fetuin/alpha2-HS glycoprotein enhances phagocytosis of apoptotic cells and macropinocytosis by human macrophages. Clin Sci 2003;105:273–278. [CrossRef]
24. Ma P, Feng YC. Decreased serum fetuin-A levels and active inflammatory bowel disease. Am J Med Sci 2014;348:47–51. [CrossRef]
25. Underhill DM, Ozinsky A, Smith KD, Aderem A. Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci U S A 1999;96:14459–14463. [CrossRef]
26. Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol 2014;14:329–342. [CrossRef]
27. Alex P, Zachos NC, Nguyen T, et al. Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflamm Bowel Dis 2009;15:341–352. [CrossRef]
28. Rovedatti L, Kudo T, Biancheri P, et al. Differential regulation of interleukin 17 and interferon gamma production in inflammatory bowel disease. Gut 2009;58:1629–1636. [CrossRef]
29. Tsukada Y, Nakamura T, Iimura M, Iizuka BE, Hayashi N. Cytokine profile in colonic mucosa of ulcerative colitis correlates with disease activity and response to granulocytapheresis. Am J Gastroenterol 2002;97:2820–2828. [CrossRef]