Hamid Asadzadeh Aghdaei1, Azade Amini Kadijani1, Dario Sorrentino2,3, Alireza Mirzaei4, Shabnam Shahrokh1, Hedieh Balaii1, Marco Geraci5, Mohammad Reza Zali6. 1. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. IBD Center, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA. 3. Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine, Italy. 4. Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran. 5. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA. 6. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract
BACKGROUND: Predicting the response of inflammatory bowel disease (IBD) patients to infliximab (IFX) is an unmet clinical need. The expression and density of transmembrane tumor necrosis factor-α in circulating leukocytes maybe directly related to response by promoting apoptosis. AIM: We tested the hypothesis that direct apoptosis assessment by real-time polymerase chain reaction evaluation of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins in peripheral blood mononuclear cells (PBMCs) might be associated with response to IFX. METHODS: IFX naïve patients (Crohn's disease, 32 and ulcerative colitis, 20; 35 responders and 17 non-responders) were evaluated for Bax and Bcl-2 mRNA expression levels before and 2 weeks after the first infusion. In a subset of patients, apoptosis was also evaluated using flow cytometry. RESULTS: After the first infusion, Bax increased more in responders than in non-responders (0.7± 0.38 vs 0.81 ± 0.32 and 0.86 ± 0.37 vs 0.87 ± 0.45, respectively, p = 0.071). Bcl-2 decreased more in responders than in non-responders (0.71 ± 0.12 vs 0.63 ± 0.13 and 0.81 ± 0.28 vs 0.77 ± 0.27, respectively, p = 0.038). The Bax/Bcl-2 ratio increased more in responders than in non-responders (0.99 ± 0.5 vs 1.3 ± 0.51 and 1.03 ± 0.17 vs 1.1 ± 0.28, respectively, p = 0.005). The Bax/Bcl-2 ratio was able to predict response in 33/52 patients and was correlated to flow cytometry-assessed apoptosis (r = 0.911; p < 0.001). CONCLUSIONS: An increased Bax/Bcl-2 ratio in PBMCs was associated with therapeutic response to IFX in IBD patients.
BACKGROUND: Predicting the response of inflammatory bowel disease (IBD) patients to infliximab (IFX) is an unmet clinical need. The expression and density of transmembrane tumor necrosis factor-α in circulating leukocytes maybe directly related to response by promoting apoptosis. AIM: We tested the hypothesis that direct apoptosis assessment by real-time polymerase chain reaction evaluation of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins in peripheral blood mononuclear cells (PBMCs) might be associated with response to IFX. METHODS: IFX naïve patients (Crohn's disease, 32 and ulcerative colitis, 20; 35 responders and 17 non-responders) were evaluated for Bax and Bcl-2 mRNA expression levels before and 2 weeks after the first infusion. In a subset of patients, apoptosis was also evaluated using flow cytometry. RESULTS: After the first infusion, Bax increased more in responders than in non-responders (0.7± 0.38 vs 0.81 ± 0.32 and 0.86 ± 0.37 vs 0.87 ± 0.45, respectively, p = 0.071). Bcl-2 decreased more in responders than in non-responders (0.71 ± 0.12 vs 0.63 ± 0.13 and 0.81 ± 0.28 vs 0.77 ± 0.27, respectively, p = 0.038). The Bax/Bcl-2 ratio increased more in responders than in non-responders (0.99 ± 0.5 vs 1.3 ± 0.51 and 1.03 ± 0.17 vs 1.1 ± 0.28, respectively, p = 0.005). The Bax/Bcl-2 ratio was able to predict response in 33/52 patients and was correlated to flow cytometry-assessed apoptosis (r = 0.911; p < 0.001). CONCLUSIONS: An increased Bax/Bcl-2 ratio in PBMCs was associated with therapeutic response to IFX in IBD patients.
Authors: J Doering; B Begue; M J Lentze; F Rieux-Laucat; O Goulet; J Schmitz; N Cerf-Bensussan; F M Ruemmele Journal: Gut Date: 2004-11 Impact factor: 23.059
Authors: Irasema Oroz-Parra; Carolina Álvarez-Delgado; Karla Cervantes-Luevano; Salvador Dueñas-Espinoza; Alexei F Licea-Navarro Journal: Mar Drugs Date: 2019-12-20 Impact factor: 5.118