Investigating the role of complement component 5a in ANCA-associated vasculitis

研究补体成分 5a 在 ANCA 相关血管炎中的作用

• 批准号: MR/Y000854/1
• 负责人: Dominic McGovern
• 金额: $ 36.79万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY000854%2F1
• 关键词: Investigating; role; complement; component; 5a; Investigating; role; complement; component; 5a

The immune system is the body's powerful response system that acts to defend us against infections. It has two main protective methods - mediated by immune cells and soluble components like 'antibodies' and 'complement' proteins which can punch holes in microbes. Unfortunately, the immune system sometimes gets wrongly activated and responds to our own tissues and organs. This causes a group of diseases called 'autoimmune' diseases. One subtype is a disease called 'vasculitis', literally meaning 'inflammation of blood vessels', which occurs as a result of immune attack by antibodies and complement. Blood vessel inflammation causes patients to get organ damage in the lungs and kidneys. Sadly, this kidney damage can be severe enough to cause kidney failure, requiring blood cleaning therapy (dialysis). The treatments that we have used for the past 20 years are variably effective, and have lots of side effects, but recently, a new drug that blocks the complement system was used in patients with vasculitis in a clinical trial. This complement blocker drug seemed to reduce kidney damage, but we don't know exactly how it does this.This project will investigate blood, kidney tissue, and tissue taken from the back of the nose that contains immune cell collections (called the adenoids). We will take these tissue samples from patients with vasculitis who come to our clinic before and after they receive the complement blocker drug. We will use new technologies to analyse antibodies and tissue cells to produce a clearer picture of the effect of blocking complement on the human immune system and kidney. One of these technologies uses information about how the genetic code of cells is translated into action, by measuring genetic messenger molecules called 'RNA'. The Clatworthy lab are international experts in studying RNA, down to the level of individual immune or tissue cells. We can also match up this information with changes in blood immune cells and kidney function and can determine the location of immune cells in tissues affected by the complement blocking drug using a special microscope technique that can measure where RNA molecules are in tissue. The information that our project will generate is important because it will tell us more about how complement affects the immune system in humans and how the complement-blocking drug works, both in inflamed kidneys and in immune tissues, potentially opening it up to be used to treat other autoimmune and kidney diseases.

免疫系统是人体强大的反应系统，可防止我们免受感染。它具有两种主要的保护方法 - 由免疫细胞和可溶成分介导的“抗体”和“补体”蛋白，它们可以在微生物中打孔。不幸的是，免疫系统有时会被错误地激活，并响应我们自己的组织和器官。这会导致一组称为“自身免疫性”疾病的疾病。一种亚型是一种称为“血管炎”的疾病，字面意思是“血管炎症”，这是由于抗体和补体的免疫发作而导致的。血管炎症会导致患者在肺和肾脏中受到器官损伤。可悲的是，这种肾脏损伤可能足以引起肾脏衰竭，需要血液清洁疗法（透析）。过去20年中我们使用的治疗方法具有可变的效果，并且具有很大的副作用，但是最近，在一项临床试验中，一种阻止补体系统的新药被用于血管炎的患者。这种补体阻滞剂药物似乎减少了肾脏的损害，但我们不知道它是如何做到的。该项目将研究从鼻子的后部提取的血液，肾脏组织和组织，其中包含免疫细胞收集（称为腺样体）。我们将从血管炎的患者中接受这些组织样品，这些血管炎在接受补体阻滞剂药物之前和之后来到我们的诊所。我们将使用新技术来分析抗体和组织细胞，以更清楚地了解阻断人类免疫系统和肾脏的影响。这些技术之一通过测量称为“ RNA”的遗传信使分子，使用有关细胞遗传密码如何转化为作用的信息。 Clatworthy Lab是研究RNA的国际专家，直至单个免疫或组织细胞的水平。我们还可以将这些信息与血液免疫细胞和肾功能的变化相匹配，并可以使用特殊的显微镜技术来确定由补体阻断药物影响的组织中的免疫细胞的位置，该技术可以测量RNA分子在组织中的位置。我们的项目将产生的信息很重要，因为它会告诉我们更多有关补体如何影响人类免疫系统的信息，以及补体阻滞药物如何在发炎的肾脏和免疫组织中起作用，有可能将其开放以治疗其他自身免疫性和肾脏疾病。