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-  2018 

An increased Bax/Bcl

DOI: 10.1177/2050640618774637

Keywords: Apoptosis,inflammatory bowel diseases,infliximab,therapeutic response

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Abstract:

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. 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. IFX na?ve 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. 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). An increased Bax/Bcl-2 ratio in PBMCs was associated with therapeutic response to IFX in IBD patients

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