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s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S129 P300 Correlation of age and serum dipeptidyl peptidase IV (DPP IV/CD26) activity in patients with inflammatory bowel diseases J. Varljen1 *, L. Baticic1, D. Detel1, N. Varljen2, B. Mijandrusic Sincic3. 1School of Medicine, Rijeka, Croatia, 2Thallassotherapija Opatija, School of Medicine, Rijeka, Croatia, 3Clinical Hospital Centre, School of Medicine, Rijeka, Croatia Crohn’s disease (CD) and ulcerative colitis (UC) are the best known forms of inflammatory bowel diseases (IBD). Their etiology is still unclear, but recent studies indicated the involvement of the immune system in the pathogenesis. Dipeptidyl peptidase IV (DPP IV/CD26) is a membrane-bound multifunctional glycoprotein, acting as a proteolytic molecule, receptor, binding and costimulatory molecule. The proteolytic cleavage of the membrane bound DPP IV results in a soluble form that migrates in the plasma. It has previously been shown that the DPP IV/CD26 could play a significant role in the pathophysiology of IBD. The aim of this study was to determine the influence of patient’s age on the serum DPP IV/CD26 activity in patients affected with IBD. The research was performed on 93 patients, divided in 2 groups: 31 young patients (mean age 13.8±1.7 years, 24 with CD and 7 with UC) and 62 adult patients (age 42.7±14.4 years, 38 with CD and 24 with UC). The control group included 111 healthy blood donors: 46 children (age 13.8±2.8 years) and 65 adults (age 41.6±12.1 years). Serum DPP IV/CD26 activities in both young and adult patients with IBD were found to be statistically sigificantly decreased when compared to their healthy controls. Values correlated inversely with the disease severity for both CD and UC. When comparing serum DPP IV/CD26 activities between young and adult patients with IBD, but even between young and adult healthy controls, it was noticed that serum DPP IV/CD26 activity decreases statistically significantly with age. The results of this study show that serum DPP IV/CD26 could be useful as an available, noninvasive marker in the diagnosis of the disease activity. This research also shows that age-related standard values should be undoubtedly established in clinical laboratory practice because of the age-dependent decrease in serum DPP IV/CD26 activity. P301 Tumor necrosis factor-alpha gene polymorphism in Russian patients with ulcerative colitis A.G. Kharitonov1 *, E.A. Kondrashina1, A.Y. Baranovsky1, Y.A. Nasykhova2, V.S. Baranov2. 1Saint-Petersburg Medical Academy of Postgraduate Education of Roszdrav, SaintPetersburg, Russian Federation, 2Ott’s Institute of Obstetrics & Gynecology, Saint-Petersburg, Russian Federation Tumor necrosis factor (TNF)-alpha play a key role in inflammatory response in Crohn’s disease and ulcerative colitis (UC). The aim of our study was to determine the effect of two single nucleotide polymorphisms (SNPs) of the TNF-alpha gene, TNF 308 G/A and TNF 238 G/A, their influence on inflammatory activity and the clinical manifestations in Russian patients with UC. Methods: The distribution of 308 and 238 TNF-alpha genotypes was analyzed in 74 patients with UC and 116 healthy controls. Results: The genotype and allelic frequency of TNF-alpha 308 in patients with UC were 18.9% and 12.2%, respectively, significantly higher than in control population (6.8% and 4.3%, respectively; p < 0.05). Carrying of 308A allele of TNF-a gene increases the UC risk (OR = 3.09). We found that patients with 308G/A genotype had higher level of platelets (p = 0.045) and more frequent arthritis (p = 0.048) in active disease compared with patients with 308G/G genotype. No difference in the G→A substitution at position 238 was observed. Conclusion: TNF-alpha 308 G/A polymorphism may play a role in UC in Russian patients, who have more intensive inflammatory activity. P302 Innate immune suppression by trace metals an unexpected role in the pathogenesis of Crohn’s disease? S. Ben-Horin *, E. Fudim, O. Picard, A. Lahat, M. Yavzori, S. Bar-Meir, Y. Chowers. Sheba Medical Center, Ramat-Gan, Israel Aim: A deficient innate immune response in the gut and ensuing excessive adaptive immune activation has been implicated in the pathogenesis of Crohn’s disease (CD), but the cause for this inadequate innate immunity has not been determined. The aim of this study was to investigate the possible role of dietary trace metals in the immunopathogenesis of CD. Methods: Peripheral blood mononuclear cells (PBMC) were obtained from CD patients (n = 17) and healthy controls (n = 13). Cellular proliferation of CD4+ T-cells, and secretion of TNF-alpha and IL-8 by PBMC were assessed after addition of beryllium, aluminum or zirconium, in the presence or absence of LPS or TSST stimulation. Apoptosis of CCD+ T-cells and CD14+ monocytes was similarly examined by AnnexinV/PI assay. Results: None of the metals stimulated proliferation of CD4+ T-cells, nor elicited cytokine secretion by PBMC. Surprisingly however, beryllium significantly and selectively reduced IL-8 secretion by LPS-activated or TSST1-triggered monocytes (893±667 vs. 409±371mcg/ml, P= 0.002), an effect that was not observed with the other metals. Importantly, this inhibition of IL-8 production was not mediated by any discernable toxic cell death or apoptosis induction. Moreover, beryllium-induced suppression of IL-8 secretion could be partially reversed by the co-incubation of cells with GM-CSF, a recently proposed agent for the treatment of CD. Conclusions: These data indicate that beryllium specifically inhibits a key cytokine in the innate immune response to bacterial LPS. This inhibitory effect could possibly undermine the immune-bacterial homeostasis in the gut, leading to excessive immune activation and ensuing chronic inflammation. P303 Peroxisome proliferator-activated receptor gamma (PPARg) expression and activation in colonic epithelial cells from patients with ulcerative colitis: a randomized, controlled pilot study of the effect of topical treatment with rosiglitazone enemas G. Pedersen1 *, J. Brynskov2. 1Department of Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark, 2Department of Gastroenterology, Herlev University Hospital, Herlev, Denmark Background and Aim: The peroxisome proliferator-activated receptor gamma (PPARg) is a nuclear hormone receptor highly expressed in normal human colon, where it attenuates inflammatory responses. Impaired PPARg expression has been described in colonic epithelial cells in animal models and in patients with active ulcerative colitis (UC), but the functional significance in humans is not well described. The primary aim of this study was to describe the expression pattern and in vitro function of PPARg in human colonic epithelium. Secondly, we examined the clinical effect of treatment with rosiglitazone enemas (a PPARg ligand) in a small controlled study in patients with active distal ulcerative colitis. Methods: Spontaneous and rosiglitazone-induced PPARgand adipophillin expression (a PPARg-activated gene) were measured by RT-PCR in primary short-term cultures of colonic epithelial cells isolated from endoscopic biopsies from controls (n = 8) and UC patients (n = 8). Fourteen UC patients with active proctitis or proctosigmoiditis were randomised by gest on N ovem er 9, 2016 http://eccoxfordjournals.org/ D ow nladed from |
