Clinical Response to Vedolizumab in Ulcerative Colitis Patients Is Associated with Changes in Integrin Expression Profiles
Clinical Response to Vedolizumab in Ulcerative Colitis Patients Is Associated with Changes in Integrin Expression Profiles
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DOI：
10.3389/fimmu.2017.00764
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发表时间：
2017-07-03
影响因子：
7.3
通讯作者：
Zundler, Sebastian
中科院分区：
文献类型：
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作者：
Fuchs, Friederike;Schillinger, Daniela;Zundler, Sebastian
背景资料：尽管取得了很大的临床成功，但对Vedolizumab治疗炎症性肠病的免疫学效应缺乏更深入的了解。特别是，在个别患者的差异临床反应的原因，对整合素表达的T细胞亚群的平衡的精确影响，以及这些问题之间可能存在的关联尚不清楚。方法：血液样本接受临床Vedolizumab治疗的患者依次收集和分析整合素和趋化因子受体的表达T细胞。此外，收集患者的临床和实验室数据，并分析归巢标记物表达和临床参数之间的变化以寻找可能的相关性。虽然在克罗恩病（CD）中未发现整合素表达变化与结局参数变化的显著相关性，但溃疡性结肠炎（UC）中α 4 β 7水平的增加似乎与有利的临床发展相关，而增加α 4 β 1和α E β 7与结果参数的负性变化相关。Vedolizumab治疗16周后评估的应答者和非应答者6周后α 4 β 1整联蛋白表达的变化存在显著差异，接受者-操作者特征分析中，以+4.2%为临界值，获得100%的灵敏度和100%的特异性。我们的数据显示，UC患者（而非CD患者）对Vedolizumab治疗的临床应答与整合素表达谱的特异性变化相关，为机制研究和可能的预测开辟了新途径。对治疗的反应。
Background: Despite large clinical success, deeper insights into the immunological effects of vedolizumab therapy for inflammatory bowel diseases are scarce. In particular, the reasons for differential clinical response in individual patients, the precise impact on the equilibrium of integrin-expressing T cell subsets, and possible associations between these issues are not clear.Methods: Blood samples from patients receiving clinical vedolizumab therapy were sequentially collected and analyzed for expression of integrins and chemokine receptors on T cells. Moreover, clinical and laboratory data from the patients were collected, and changes between homing marker expression and clinical parameters were analyzed for possible correlations.Results: While no significant correlation of changes in integrin expression and changes in outcome parameters were identified in Crohn's disease (CD), increasing alpha 4 beta 7 levels in ulcerative colitis (UC) seemed to be associated with favorable clinical development, whereas increasing alpha 4 beta 1 and alpha E beta 7 correlated with negative changes in outcome parameters. Changes in alpha 4 beta 1 integrin expression after 6 weeks were significantly different in responders and non-responders to vedolizumab therapy as assessed after 16 weeks with a cutoff of +4.2% yielding 100% sensitivity and 100% specificity in receiver-operator-characteristic analysis.Discussion: Our data show that clinical response to vedolizumab therapy in UC but not in CD is associated with specific changes in integrin expression profiles opening novel avenues for mechanistic research and possibly prediction of response to therapy.