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Decoy receptor 3: its role as biomarker for chronic inflammatory diseases

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World Journal of immunology 2013年第3期3卷 44-53页

作者： spyros i siakavellas Giorgos Bamias Academic Department of Gastroenterology Ethnikon and Kapodistriakon University Laikon Hospital 11527 Athens Greece

Members of the tumor-necrosis factor-α(TNF-α) and TNF-α receptor(TNFR) superfamilies of proteins(TNFSF and TNFRSF, respectively) play important roles in the function of the immune system. Decoy receptor 3(Dc R3, TNFRSF6b) is a decoy receptor that binds to three TNFSF ligands, Fas L, LiGHT and TL1 A. Association to these ligands competes with the corresponding functional receptors and blocks downstream signaling, leading to immunomodulatory effects, including the prevention of apoptosis. Dc R3 lacks a transmembrane region and exists only as a secreted protein, which is detectable in biological fluids. Recent studies have shown that Dc R3 is upregulated and may be pathogenetically implicated in several and diverse chronic inflammatory diseases. The strongest associations have been described for rheumatological diseases, mainly systemic lupus erythematosus and rheumatoid arthritis, inflammatory bowel disease, and serious infectious conditions, including systemic inflammatory response syndrome. in the majority of these conditions, Dc R3 m RNA and protein expression is elevated both at the target tissues as well as in the systemic circulation. Dc R3 concentration in the serum is untraceable in the majority of healthy individuals but can be detected in patients with various inflammatory diseases. in mostsuch cases, soluble Dc R3 correlates with disease severity, as patients with severe forms of disease have significantly higher levels than patients with milder or no activity. in addition, effective anti-inflammatory treatment leads to the disappearance of soluble Dc R3 from the circulation. Taken together, current evidence suggests that serum Dc R3 may become a useful biomarker for chronic inflammatory disorders, as it is upregulated in response to inflammatory stimuli, and may serve both as a prognostic marker for disease severity and as a surrogate indicator of response to treatment.

关键词： Decoy receptor 3 Tumor necrosis factor receptor superfamily of proteins Chronic inflammation infection Disease activity Biomarker

Early ileocolonoscopy with biopsy for the evaluation of persistent post-transplantation diarrhea

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World Journal of Gastroenterology 2010年第30期16卷 3834-3840页

作者： Giorgos Bamias John Boletis Theodoros Argyropoulos Chrysanthi Skalioti spyros i siakavellas ioanna Delladetsima irene Zouboulis-Vafiadis George L Daikos Spiros D Ladas Gastroenterology Division 1st Department of Internal MedicinePropaedeuticMedical SchoolUniversity of Athens"Laikon" Hospital11527AthensGreece Department of Nephrology and Renal Transplantation Unit "Laikon" Hospital11527AthensGreece 1st Department of Pathology University of Athens"Laikon"Hospital11527AthensGreece

AiM: To investigate the signifi cance of ileocolonoscopy with histology in the evaluation of post-transplantation persistent diarrhea (PD). METHODS: We retrospectively reviewed all records of renal transplant patients with PD, over a 3-year period. All patients were referred for ileocolonoscopy with biopsy, following a negative initial diagnostic work up. Clinical and epidemiological data were compared between cases with infectious or drug-induced diarrhea. RESULTS: We identif ied 30 episodes of PD in 23 renaltransplant patients (1-3 cases per patient). There were 16 male patients and the mean age at the time of PD was 51.4 years. The average time from transplantation to a PD episode was 62.3 ± 53.2 mo (range 1-199 mo). ileocolonoscopy detected mucosal abnormalities in 19 cases, whereas the intestinal mucosa appeared normal in 11 cases. Histological examination achieved a specific diagnosis in 19/30 cases (63.3%). in nine out of 11 cases (82%) with normal endoscopic appearance of the mucosa, histological examination of blinded biopsies provided a specif ic diagnosis. The etiology of PD was infectious in 11 cases (36.6%), drug-related in 10 (33.3%), of other causes in three (10%), and of unknown origin in six cases (20%). infectious diarrhea occurred in significantly longer intervals from transplantation compared to drug-related PD (85.5 ± 47.6 mo vs 40.5 ± 44.8 mo, P ingly, PD due to drug-toxicity was rarely seen after the f irst year post-transplantation. Clinical improvement followed therapeutic intervention in 90% of cases. Modif ication of immunosuppressive regimen was avoided in 57% of patients. CONCLUSiON: Early ileocolonoscopy with biopsies from both affected and normal mucosa is an important adjunctive tool for the etiological diagnosis of PD in renal transplant patients.

关键词： Endoscopy Post-transplantation diarrhea Histology Enteric infections Mycophenolate mofetilcolitis

Fecal calprotectin measurement is a marker of shortterm clinical outcome and presence of mucosal healing in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2017年第41期23卷 7387-7396页

作者： Athanasios Kostas spyros i siakavellas Charalambos Kosmidis Anna Takou Joanna Nikou Georgios Maropoulos John Vlachogiannakos George V Papatheodoridis ioannis Papaconstantinou Giorgos Bamias Department of Gastroenterology University of Athens Medical School Laiko General Hospital Bioche-mistry Department Laiko General Hospital 2nd Department of Surgery University of Athens Medical School Areteion General Hospital

AiM To evaluate the utility of fecal calprotectin(FC) in predicting relapse and endoscopic activity during follow-up in an inflammatory bowel disease(iBD) *** All FC measurements that were obtained during a 3-year period from patients with inflammatory bowel disease in clinical remission were identified. Data regarding the short-term(6 mo) course of the disease were extracted from the medical files. Exclusion criteria were defined as:(1) An established flare of the disease at the time of FC measurement,(2) Loss to follow up within 6 mo from baseline FC measurement, and,(3) insufficient data on file. Statistical analysis was performed to evaluate whether baseline FC measurement could predict the short term clinical relapse and/or the presence of mucosal *** We included 149 [Crohn's disease(CD) = 113, Ulcerative colitis(UC) = 36, male = 77] iBD patients in our study. Within the determined 6-month period post-FC measurement, 47(31.5%) had a disease flare. Among 76 patients who underwent endoscopy, 39(51.3%) had mucosal healing. Baseline FC concentrations were significantly higher in those who had clinical relapse compared to those who remained in remission during follow up(481.0 μg/g, 286.0-600.0 vs 89.0, 36.0-180.8, P ignificant predictive value of baseline median with iQR FC for clinical relapse was confirmed by multivariate Cox analysis [HR for 100μg/g: 1.75(95%Ci: 1.28-2.39), P = 0.001]. Furthermore, lower FC baseline values significantly correlated to the presence of mucosal healing in endoscopy(69.0 μg/g, 30.0-128.0 vs 481.0, 278.0-600.0, in those with mucosal inflammation, median with iQR, P ion with a high sensitivity and specificity for predicting clinical relapse(261 μg/g with AUC = 0.901, sensitivity 87.2%, specificity 85.3%, P ing(174 μg/g with AUC = 0.956, sensitivity 91.9%, specificity 87.2%, P in

关键词： Fecal calprotectin Biomarker inflammatory bowel disease Mucosal healing Clinical outcome Relapse Ulcerative colitis Crohn’s disease

Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis

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World Journal of Gastrointestinal Pathophysiology 2014年第3期5卷 293-303页

作者： Evanthia Zampeli Michalis Gizis spyros i siakavellas Giorgos Bamias Gastroenterology Department Alexandra General Hospital Academic Department of Gastroenterology Ethnikon and Kapodistriakon University of Athens Laikon Hospital

Ulcerative colitis(UC) is an immune-mediated, chronic inflammatory disease of the large intestine. its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor(anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve(primary non-response) or lose response after a period of improvement(secondary non-response/loss of response). in addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters thatmay predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular(immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy.

关键词： Ulcerative colitis infliximab Adalimumab Anti-tumor necrosis factor Predictors of response Personalized treatment

Liver cirrhosis-effect on QT interval and cardiac autonomic nervous system activity

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World Journal of Gastrointestinal Pathophysiology 2018年第1期9卷 28-36页

作者： Elias Tsiompanidis spyros i siakavellas Anastasios Tentolouris ioanna Eleftheriadou Stamatia Chorepsima Anastasios Manolakis Konstantinos Oikonomou Nikolaos Tentolouris First Department of Propaedeutic internal Medicine Medical School National and Kapodistrian University of Athens Laiko General Hospital

AiM To examine the impact of liver cirrhosis on QT interval and cardiac autonomic neuropathy(CAN). METHODS A total of 51 patients with cirrhosis and 51 controls were examined. Standard 12-lead electrocardiogram recordings were obtained and QT as well as corrected QT interval(QTc) and their dispersions(dQT, dQTc) were measured and calculated using a computer-based program. The diagnosis of CAN was based upon the battery of the tests proposed by Ewing and Clarke and the consensus statements of the American Diabetes Association. CAN was diagnosed when two out of the four classical Ewing tests were abnormal. RESULTS QT, QTc and their dispersions were significantly longer(P in patients with cirrhosis than in controls. No significant differences in QT interval were found among the subgroups according to the etiology of cirrhosis. Multivariate regression analysis after controlling for age, gender and duration of cirrhosis demonstrated significant association between QT and presence of diabetes mellitus [standardized regression coefficient(beta) = 0.45, P = 0.02] and treatment with diuretics(beta = 0.55, P = 0.03), but not with the Child-Pugh score(P = 0.54). Prevalence of CAN was common(54.9%) among patients with cirrhosis and its severity was associated with the Child-Pugh score(r = 0.33, P = 0.02). Moreover, patients with decompensated cirrhosis had more severe CAN that those with compensated cirrhosis(P = 0.03). No significant association was found between severity of CAN and QT interval *** Patients with cirrhosis have QT prolongation. Treatment with diuretics is associated with longer QT. CAN is common in patients with cirrhosis and its severity is associated with severity of the disease.

关键词： QT interval Cardiac autonomic neuropathy Cirrhotic cardiomyopathy Child-Pugh score Model for end-stage liver disease score Liver cirrhosis