Murat KEKİLLİ, Alpaslan TANOĞLU, Fatih KARAAHMET, Zeynal DOĞAN, Murat CAN, Abdurrahim SAYILIR, Başak ÇAKAL, Tolga DÜZENLİ, Yavuz BEYAZİT

Midkine level may be used as a noninvasive biomarker in Crohn's disease

Background/aim: Crohn's disease CD is a kind of inflammatory bowel disease. Midkine MDK is an endogenous inflammatory marker. We aimed to investigate the relationship between MDK levels and inflammation and hence determine whether MDK can be used as a noninvasive biomarker in active CD. Materials and methods: Sixty-five consecutive patients over the age of 18 with CD and 36 healthy controls were included in this study. CD patients' venous blood samples were taken before treatment. Serum MDK levels were determined in human plasma samples by enzyme-linked immunosorbent assay ELISA method. Results: The mean age of the study patients was 44.8 ± 12.5 years, 35 patients were female, and 30 were male. Of these 65 patients, 37 had active CD and 28 were in the remission phase. MDK levels were significantly higher in active and remission CD than in healthy controls P = 0.01, P = 0.038, respectively . Conclusion: We report that there is an association between MDK levels and CD activation, and therefore with enhanced inflammation. MDK levels were significantly correlated with inflammatory indices. In line with our findings, we suggest the theory that MDK inhibitors may be useful in treating Crohn's disease.

Keywords:

Midkine, inflammatory bowel disease, Crohn's disease, biomarker, inflammation,

PDF

___

1. Karaahmet F, Kilincalp S, Akinci H, Hamamci M, Coban S, Yuksel I. A disease affecting all ages: Crohn’s disease. Journal of the American Geriatrics Society 2014; 62: 1200-1201.
2. Garamszegi M. Extraintestinal manifestations of inflammatory bowel diseases and their management. Orvosi Hetilap 2011; 152: 663-671.
3. Canavan C, Abrams KR, Hawthorne B, Mayberry JF. Longterm prognosis in Crohn’s disease: an epidemiological study of patients diagnosed more than 20 years ago in Cardiff. Alimentary Pharmacology & Therapeutics 2007; 25: 59-65.
4. Peluso I, Pallone F, Monteleone G. Interleukin-12 and Th1 immune response in Crohn’s disease: pathogenetic relevance and therapeutic implication. World Journal of Gastroenterology 2006; 12: 5606-5610.
5. Abraham C, Cho JH. Inflammatory bowel disease. New England Journal of Medicine 2009; 361: 2066-2078.
6. Sakamoto K, Kadomatsu K. Midkine in the pathology of cancer, neural disease, and inflammation. Pathology International 2012; 62: 445-455
7. Weckbach LT, Muramatsu T, Walzog B. Midkine in inflammation. Scientific World Journal 2011; 11: 2491-2505.
8. Oppman B, Lesley R, Blom B, Timans JC, Xu Y et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000; 13: 715-725.
9. Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. Journal of Experimental Medicine 2006; 203: 2473-2483.
10. Yuki T, Ishihara S, Rumi MAK, Ortega-Cava CF, Kadowaki Y et al. Increased expression of midkine in the rat colon during healing of experimental colitis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2006; 291: G735-743.
11. Dignass A, Van Assche G, Lindsay JO, Lémann M, Söderholm 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: current management. Journal of Crohn’s and Colitis 2010; 4: 28-62.
12. Strober W, Fuss IJ. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology 2011; 140: 1756-1767.
13. Sanchez-Munoz F, Dominguez-Lopez A, Yamamoto-Furusho JK. Role of cytokines in inflammatory bowel disease. World Journal of Gastroenterology 2008; 14: 4280-4288.
14. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. Journal of Biological Chemistry 2003; 278: 1910-1914.
15. Krzystek-Korpacka M, Neubauer K, Matusiewicz M. Circulating midkine in Crohn’s disease: clinical implications. Inflammatory Bowel Diseases 2010; 16: 208-215.
16. Krzystek-Korpacka M, Neubauer K, Matusiewicz M. Clinical relevance of circulating midkine in ulcerative colitis. Clinical Chemistry and Laboratory Medicine 2009; 47: 1085-1090.
17. Ibusuki M, Fujimori H, Yamamoto Y, Ota K, Ueda M et al. Midkine in plasma as a novel breast cancer marker. Cancer Science 2009; 100: 1735-1739.