Open AccessAn increased Bax/Bcl‐2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients
Author(s) -
Aghdaei Hamid Asadzadeh,
Kadijani Azade Amini,
Sorrentino Dario,
Mirzaei Alireza,
Shahrokh Shabnam,
Balaii Hedieh,
Geraci Marco,
Zali Mohammad Reza
Publication year - 2018
Publication title -
ueg journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.667
H-Index - 35
eISSN - 2050-6414
pISSN - 2050-6406
DOI - 10.1177/2050640618774637
Subject(s) - medicine , infliximab , apoptosis , inflammatory bowel disease , flow cytometry , ulcerative colitis , peripheral blood mononuclear cell , tumor necrosis factor alpha , gastroenterology , immunology , disease , in vitro , biochemistry , chemistry
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.