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

免疫系统是人体强大的反应系统，可以保护我们免受感染。它有两种主要的保护方法——由免疫细胞和可溶性成分介导，如“抗体”和“补体”蛋白质，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，并对我们自己的组织和器官做出反应。这导致了一系列被称为“自身免疫性”疾病的疾病。其中一种亚型是一种叫做“血管炎”的疾病，字面意思是“血管炎症”，是抗体和补体免疫攻击的结果。血管炎症会导致患者肺部和肾脏器官受损。可悲的是，这种肾脏损害严重到足以导致肾衰竭，需要血液净化治疗（透析）。在过去的20年里，我们使用的治疗方法效果不一，而且有很多副作用，但最近，一种阻断补体系统的新药被用于血管炎患者的临床试验。这种补体阻滞剂药物似乎可以减少肾脏损害，但我们不知道它是如何做到的。该项目将研究血液、肾脏组织和从鼻子后部提取的含有免疫细胞集合（称为腺样体）的组织。我们将从血管炎患者在接受补体阻滞剂药物前后到我们诊所采集这些组织样本。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补体对人体免疫系统和肾脏的影响。其中一项技术通过测量被称为“RNA”的遗传信使分子，利用有关细胞遗传密码如何转化为行动的信息。克拉特沃西实验室是研究RNA的国际专家，研究范围一直延伸到个体免疫细胞或组织细胞的水平。我们还可以将这些信息与血液免疫细胞和肾脏功能的变化相匹配，并可以使用一种特殊的显微镜技术来确定受补体阻断药物影响的组织中免疫细胞的位置，这种技术可以测量RNA分子在组织中的位置。我们的项目将产生的信息很重要，因为它将告诉我们更多关于补体如何影响人体免疫系统以及补体阻断药物如何在发炎的肾脏和免疫组织中起作用的信息，有可能将其用于治疗其他自身免疫性疾病和肾脏疾病。

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.