Role of pharmacological activity of autoantibodies in ME/CFS

自身抗体药理活性在 ME/CFS 中的作用

• 批准号: MR/Y003667/1
• 负责人: Dmitry Veprintsev
• 金额: $ 52.09万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY003667%2F1
• 关键词: Role; pharmacological; activity; autoantibodies; ME

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a condition characterised by extreme fatigue, memory impairment, pain and other symptoms that vary from patient to patient. It affects about 0.9% of the population and is often triggered by an acute viral or bacterial infection, such as Epstein-Barr virus. The underlying physiological and molecular basis of ME/CFS is unknown, and no effective treatments exist. One proposed mechanism is that the blood flow is altered by autoantibodies against receptors involved in blood flow regulation. Antibodies are generated by the immune system to recognise intruders and under normal conditions, our immune system is trained not to attack our own tissues. However, during a severe infection, the immune system adopts an "all hands on deck" approach, which results in some of the newly-produced antibodies escaping quality control and targeting our own tissues, autoantibodies. Receptors regulation blood flow are located in walls of blood vessels and cause a blood vessel to dilate or contract as the demand for oxygen and nutrients to tissues such as the brain or muscles changes. Research has found increased levels of these autoantibodies in ME/CFS patients and initial trials removing these autoantibodies from the blood using a technique called immunoadsorption have shown improvement in symptoms. In this project, we will test the hypothesis that autoantibodies can activate or inhibit the receptors responsible for the blood flow regulation, in a similar way medical drugs are used to regulate blood pressure. We aim to profile serum samples from 325 ME/CFS patients and 130 healthy individuals to determine the presence of autoantibodies against all thirty receptors involved in blood pressure regulation. Importantly, we will study the ability of autoantibodies detected in each sample to activate or inhibit these receptors in order to test the hypothesis that the activity of these autoantibodies is a decisive factor in the disease. If our hypothesis is correct, we will be able to develop an accurate blood test that may be able to detect ME/CFS earlier or to independently confirm the diagnosis. Ultimately, we hope that these results may also indicate a possible route for therapeutic intervention to counteract the effects of autoantibodies and alleviate the ME/CFS symptoms using a combination of already existing drugs, specific for each individual case.

肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种以极度疲劳、记忆障碍、疼痛和其他症状为特征的疾病，患者之间存在差异。约0.9%的人患有此病，通常由急性病毒或细菌感染引发，如爱泼斯坦-巴尔病毒。ME/CFS的潜在生理和分子基础尚不清楚，也没有有效的治疗方法。一种被提出的机制是，血液流动是由自身抗体对参与血流调节的受体所改变的。免疫系统产生抗体来识别入侵者，在正常情况下，我们的免疫系统被训练成不攻击我们自己的组织。然而，在严重感染期间，免疫系统采取“全员参与”的方式，导致一些新产生的抗体逃脱质量控制，瞄准我们自己的组织，即自身抗体。调节血流的受体位于血管壁上，当大脑或肌肉等组织对氧气和营养物质的需求发生变化时，受体会导致血管扩张或收缩。研究发现，在ME/CFS患者中，这些自身抗体的水平有所增加，使用免疫吸附技术从血液中去除这些自身抗体的初步试验显示，症状有所改善。在这个项目中，我们将测试一个假设，即自身抗体可以激活或抑制负责血流调节的受体，就像医疗药物用来调节血压一样。我们的目标是分析325名ME/CFS患者和130名健康个体的血清样本，以确定针对所有参与血压调节的30种受体的自身抗体的存在。重要的是，我们将研究在每个样本中检测到的自身抗体激活或抑制这些受体的能力，以检验这些自身抗体的活性是疾病的决定性因素的假设。如果我们的假设是正确的，我们将能够开发出一种准确的血液测试，可能能够更早地发现ME/CFS或独立确认诊断。最终，我们希望这些结果也可以为治疗干预提供一条可能的途径，以抵消自身抗体的影响，并使用现有药物的组合来缓解ME/CFS症状，具体到每个病例。