An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients
An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients
复制标题
DOI：
10.1177/2050640618774637
复制
发表时间：
2018-08-01
影响因子：
6
通讯作者：
Zali, Mohammad Reza
中科院分区：
文献类型：
--
作者：
Aghdaei, Hamid Asadzadeh;Kadijani, Azade Amini;Zali, Mohammad Reza
背景：预测炎症性肠病（IBD）患者对英夫利西单抗（IFX）的反应是一个未满足的临床需求。跨膜肿瘤坏死因子-α在循环白细胞中的表达和密度可能与通过促进凋亡的反应直接相关。目的：我们测试了通过实时聚合酶链反应评价外周血单核细胞（PBMC）中促凋亡（Bax）和抗凋亡（Bcl-2）蛋白的直接凋亡评估可能与IFX反应相关的假设。IFX初治患者（克罗恩病，32例和溃疡性结肠炎，20例; 35例应答者和17例无应答者）在首次输注前和输注后2周评价Bax和Bcl-2 mRNA表达水平。在一个子集的患者，细胞凋亡也进行了评估，使用流式细胞仪。结果：第一次输注后，Bax增加更多的反应比在无反应（0.7 +/- 0.38比0.81 +/- 0.32和0.86 +/- 0.37比0.87 +/- 0.45，分别为，p= 0.071）。Bcl-2在应答者中比在无应答者中降低更多（分别为0.71 +/- 0.12 vs 0.63 +/- 0.13和0.81 +/- 0.28 vs 0.77 +/- 0.27，p= 0.038）。Bax/BcI-2比值在应答者中比在无应答者中增加更多（分别为0.99 +/- 0.5 vs 1.3 +/- 0.51和1.03 +/- 0.17 vs 1.1 +/- 0.28，p= 0.005）。Bax/Bcl-2比值能够预测33/52例患者的反应，并且与流式细胞术评估的细胞凋亡相关（r= 0.911; p < 0.001）。
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-alpha 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 proapoptotic (Bax) and anti-apoptotic (Bcl-2) proteins in peripheral blood mononuclear cells (PBMCs) might be associated with response to IFX.Methods: IFX naive 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/BcI-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.