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Serum Dipeptidyl Peptidase IV (DPP IV/CD26) Activity in Patients with Inflammatory Bowel Diseases

The inflammatory bowel diseases (IBDs) are defined by chronic, relapsing intestinal inflammation of obscure origin. Two distinct disorders, Crohn's disease (CD) and ulcerative colitis (UC), have been identified. The etiology and pathogenesis of IBD is not well understood yet, but each disorder appears to have its own constellation of genetic factors, immunological characteristics and pathological findings. The dipeptidyl peptidase IV (DPP IV/CD26 ; EC 3.4.14.5) is an abundant, widely distributed serine protease that is able to cleave the N-terminal dipeptides from polypeptides. The cleavage by DPP IV can result in activation, inactivation or even significant change in the activity of physiological peptides. This membrane-bound glycoprotein is a unique multifunctional protein, acting as a receptor, binding and proteolitic molecule, also expressed on the surface of various cell types, including epithelial and endothelial cells and lymphocytes. The proteolytic cleavage of the membrane bound DPP IV results in a soluble form that migrates as a homodimer with a molecular weight range of 210-290 kDa. It has previously been shown that the DPP IV could play a significant role in the pathophysiology of IBD. The aim of this study was to evaluate the clinical relevance of the changes in serum DPP IV activity in adult patients with inflammatory bowel diseases (CD and UC) compared with the levels in healthy controls. We hypothesized that changes in DPP IV serum activity could relate to the disease activity together with other inflammatory parameters. In clinical practice, the differential diagnosis of CD and UC is often difficult. Different biochemical, clinical, endoscopic, pathological and histological features should be combined in order to allocate the appropriate diagnosis. However, in about 10 to 20 % of patients with cronic colitis the precise diagnosis is not possible, which results in the designation &#8220; indeterminate colitis&#8221; . The immuno-pathological bases of CD and UC pathogenesis are different. The Th1-inflammatory response induces a transmural CD-like inflammatory reaction while a Th2-cytokine profile induces an UC-like inflammation. The CD26/DPP IV signal transduction function is directly related to its expression level on human Th1 and Th2 enhancing Th1 cytokine response. Based on those findings, we furthermore hypothesized that the serum DPP IV activity could be a potential distinguishing marker between Crohn´ s disease and Ulcerative colitis. The study was performed on 62 patients, 38 with CD (mean age +/- SD 42.7 +/- 14.4 ; 19 males, 19 females), and 24 with UC (mean age +/- SD 45.6 +/- 17.6 ; 13 males, 11 females). The control group included 65 healthy donors (mean age +/- SD 41.6 +/- 12.1 ; 32 males, 33 females). The CD activity was evaluated using the Crohn´s Disease Activity Index (CDAI), while the UC activity was evaluated by the Truelove and Witts&#8217; (TW) classification. All blood samples were obtained after all patients and controls gave signed informed consent under the protocols approved by the Ethics Committee. Serum DPP IV activity has been measured spectrophotometrically according to the protocol of Kreisel et al.. The results of this study shown that both serum DPP IV activities in patients with CD (36.8 &#177; ; ; 1.5) / (&#956; mol min-1 dm-3) and UC (33.9 &#177; ; ; 2.1) / (&#956; mol min-1 dm-3) were statistically significantly decreased compared to healthy controls (48.4 &#177; ; ; 1.1) / (&#956; mol min-1 dm-3), (p<0.001), as shown on figure 1. The obtained results can suggest a functional compartmentalization of DPP IV, which can be interpreted as adaptive systemic immune response to a local inflammatory reaction. The serum DPP IV activity in IBD patients correlated inversely with the grade of diseases. No statistically significant difference in the serum DPP IV activity in patients with CD and UC was found. Therefore, it can be concluded that the DPP IV activity could not be a good marker for the differential diagnosis of those diseases. However, the soluble DPP IV in serum seems to be involved in the pathophysiology of IBD and appear to be useful as an available, non-invasive marker in the diagnosis of disease activity.

Dipeptidyl peptidase IV (DPP IV/CD26); Inflammatory bowel diseases

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