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Interrogating host immunity to predict treatment response in inflammatory bowel disease.
Nature Reviews Gastroenterology & Hepatology ( IF 45.9 ) Pub Date : 2019-11-25 , DOI: 10.1038/s41575-019-0228-5
Jonathan L Digby-Bell 1 , Raja Atreya 2 , Giovanni Monteleone 3 , Nick Powell 1, 4
Affiliation  

IBD treatment is undergoing a transformation with an expanding repertoire of drugs targeting different aspects of the immune response. Three novel classes of drugs have emerged in the past decade that target leukocyte trafficking to the gut (vedolizumab), neutralize key cytokines with antibodies (ustekinumab) and inhibit cytokine signalling pathways (tofacitinib). In advanced development are other drugs for IBD, including therapies targeting other cytokines such as IL-23 and IL-6. However, all agents tested so far are hampered by primary and secondary loss of response, so it is desirable to develop personalized strategies to identify which patients should be treated with which drugs. Stratification of patients with IBD by clinical parameters alone lacks sensitivity, and alternative modalities are now needed to deliver precision medicine in IBD. High-resolution profiling of immune response networks in individual patients is a promising approach and different technical platforms, including in vivo real-time molecular endoscopy, tissue transcriptomics and germline genetics, are promising tools to help predict responses to specific therapies. However, important challenges remain regarding the clinical utility of these technologies, including their scalability and accessibility. This Review focuses on unravelling some of the complexity of mucosal immune responses in IBD pathogenesis and how current and emerging analytical platforms might be harnessed to effectively stratify and individualise IBD therapy.

中文翻译:

询问宿主免疫以预测炎症性肠病的治疗反应。

IBD 治疗正在经历转型,针对免疫反应不同方面的药物种类不断增加。在过去十年中出现了三类新型药物,它们针对白细胞转运到肠道(维多珠单抗)、用抗体中和关键细胞因子(乌司奴单抗)和抑制细胞因子信号通路(托法替尼)。其他用于 IBD 的药物处于高级开发阶段,包括针对其他细胞因子(如 IL-23 和 IL-6)的疗法。然而,迄今为止测试的所有药物都受到原发性和继发性反应丧失的阻碍,因此需要制定个性化策略来确定哪些患者应该接受哪些药物治疗。仅通过临床参数对 IBD 患者进行分层缺乏敏感性,现在需要替代方式在 IBD 中提供精准医疗。对个体患者的免疫反应网络进行高分辨率分析是一种很有前途的方法,不同的技术平台,包括体内实时分子内窥镜检查、组织转录组学和生殖细胞遗传学,是帮助预测对特定疗法的反应的有前途的工具。然而,在这些技术的临床实用性方面仍然存在重大挑战,包括它们的可扩展性和可访问性。本综述的重点是揭示 IBD 发病机制中黏膜免疫反应的一些复杂性,以及如何利用当前和新兴的分析平台对 IBD 治疗进行有效分层和个体化。组织转录组学和生殖系遗传学是帮助预测对特定疗法的反应的有前途的工具。然而,在这些技术的临床实用性方面仍然存在重大挑战,包括它们的可扩展性和可访问性。本综述的重点是揭示 IBD 发病机制中黏膜免疫反应的一些复杂性,以及如何利用当前和新兴的分析平台对 IBD 治疗进行有效分层和个体化。组织转录组学和生殖系遗传学是帮助预测对特定疗法的反应的有前途的工具。然而,在这些技术的临床实用性方面仍然存在重大挑战,包括它们的可扩展性和可访问性。本综述的重点是揭示 IBD 发病机制中黏膜免疫反应的一些复杂性,以及如何利用当前和新兴的分析平台对 IBD 治疗进行有效分层和个体化。
更新日期:2019-11-26
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