精密医学 immunology: targeting underlying biology-澳门在线赌城娱乐

发表 2022年11月11日

所有的故事

主题:

疾病的理解

Next generation therapeutics

写的:

塔蒂阿娜支持

Executive Director and Head of Bioscience 免疫学, AstraZenca

亚当·普拉特

Vice President and Head of Translational Science and Experimental Medicine, 呼吸与免疫学, 澳门在线赌城娱乐

Building on decades of research, 澳门第一赌城在线娱乐正在开始解开复杂的炎症细胞信号通路，并揭示导致免疫介导疾病失衡的关键驱动因素.

With an estimated 5 million people worldwide living with 红斑狼疮¹ 和6.8 million with inflammatory bowel disease², well-known immune-mediated diseases, 迫切需要新的创新疗法来帮助改善这些患者的预后.

Precisely targeting disease drivers in immune-mediated diseases

Moving away from the traditional stepwise treatment approach, 下一波治疗发现正在拥抱精准医疗所能提供的潜力——确保找到合适的病人, 吃对了药, 在适当的时候. 澳门第一赌城在线娱乐正在迅速建立澳门第一赌城在线娱乐的疾病生物标志物知识，以帮助在单一疾病中区分患者亚群, and develop diagnostic tests and precision medicines, which are targeted to the underlying causes of disease.

What is precision medicine in chronic diseases?

炎症性肠病

澳门第一赌城在线娱乐在炎症性肠病(IBD)中的精准医疗方法侧重于通过识别疾病的生物标志物来选择不同的患者亚群. IBD是胃肠道慢性炎症的总称，包括溃疡性结肠炎和克罗恩病. 到目前为止, our core research has focused on inflammatory cytokines called interleukins, known to be increased in these conditions, so we can identify patients who are failing to respond to treatment or become intolerant over time³.

促炎细胞因子白介素23 (IL-23)是已知的炎症驱动因子，主要由活化的巨噬细胞和位于皮肤等组织中的树突状细胞分泌, lung and the intestinal mucosa³. IL-23通过增加辅助性T细胞(Th)来增强局部炎症，而辅助性T细胞在IBD中负责许多自身免疫反应. 克罗恩病是由Th1/Th17相互作用驱动的，其中IL-23起关键作用，这得到全基因组关联研究的支持，该研究将IL-23与克罗恩病的发病机制紧密联系起来.

The levels of IL-23 in the blood, even when elevated in disease, are hard to detect with easy-to-use technologies. An alternative biomarker is needed to clinically determine patients who have IL-23 driven disease. 效应细胞因子IL-22是IL-23的下游产物，具有维持粘膜屏障完整性和刺激上皮细胞增殖的作用. 它也是IL-23活性的直接指标，因此具有作为疾病生物标志物的潜力³.

澳门第一赌城在线娱乐认为IL-22水平的显著降低可能表明疾病活动性和治疗后潜在的疾病改变. In collaboration with Roche Diagnostics, we are currently progressing the development of an accurate, IL-22的非侵入性诊断测试，并在广泛的患者中探索生物标志物水平与临床结果之间的联系.

系统性红斑狼疮

系统性红斑狼疮 SLE是一种复杂的疾病, chronic disease in which the body’s immune system attacks healthy tissue in any part of the body. It is estimated that at least five million people worldwide have a form of 红斑狼疮¹, which can manifest in a range of symptoms including skin rash, joint pain, swelling and fevers. 红斑狼疮 remains poorly understood and the significant physical, emotional and socio-economic burden remains high for people living with the disease⁴.

SLE involves over activity of B-cells, t细胞和树突状细胞, as well as inflammatory cytokines such as type 1 interferons (IFN), IL-6 and B-cell activating factor. 细胞因子调节和协调整体炎症反应，在SLE患者中过度生产导致自身免疫反应延长, 导致受伤, inflammation and long-term organ damage^5-10.

研究表明，IFN基因特征升高与疾病之间存在关联，IFN蛋白水平与SLE的血清学和临床表现之间也存在关联¹¹. 这些数据强调了澳门第一赌城在线娱乐对IFN作为SLE疾病活动性生物标志物的关注，并有助于指导澳门第一赌城在线娱乐的精准医学方法. 研究表明，通过测量IFN mRNA水平而不是蛋白质，可以在澳门第一赌城在线娱乐的患者队列中超过四分之三的成年人中检测到IFN基因升高的特征¹². 澳门第一赌城在线娱乐已经成功地在临床研究项目中部署了这种基于血液的IFN活性生物标志物测试，以对SLE患者进行分层，并了解其潜在的疾病驱动因素¹².

前进, 澳门第一赌城在线娱乐的科学家也在研究其他免疫介导的疾病，在这些疾病中，IFN基因标记可能会丰富患者群体，可能从靶向治疗中受益，并改善他们的疾病结果.

Bringing precision medicines to patients

There remains a huge unmet need for patients and healthcare systems in immune-mediated diseases. 提供针对潜在疾病的常规诊断和精准药物将有力地促进患者获得更好的治疗结果和更可持续的护理. 创新融资, regulatory and clinical mechanisms will be necessary to support access and uptake. 澳门第一赌城在线娱乐致力于与免疫学界合作，实现这一潜力，并提供精准医学研究，以改善免疫介导性疾病患者的生活.