A BIOMARKER AND PATHWAY DISCOVERY PROGRAMME IN INFLAMMATORY DISEASE

5%到10%的人会在一生中的某个时候患上自身免疫性疾病或炎症性疾病。这些疾病的表现因人而异，有些人有严重的病程，而另一些人则有较良性的疾病。当这类疾病出现时，医生需要“盲目”治疗——因为他们无法预测哪些患者是自然良性疾病，只需要最少的治疗，哪些患者需要更密集的治疗来获得控制。这对病人和医疗系统来说都是一个大问题。这意味着需要强化治疗的患者往往发现需要推迟治疗，直到疾病进展，需要这种治疗变得明显。相反，早期不加区分地使用这些疾病的治疗可能意味着，那些本来不需要这种治疗就能好起来的人接受了不必要的治疗，使他们面临严重的副作用。这种缺乏针对性的治疗也浪费了有限的NHS资源。我们将使用尖端的“基因组”技术来测量患有多种疾病的患者在治疗前后白细胞中表达的基因。使用先进的计算技术分析这些基因表达数据将使我们能够识别使用常规临床评估不明显的患者亚群，并确定这些亚群是否与不同的疾病结果相关。可以根据这些观察结果开发的其他测试可能有助于罕见疾病患者的早期诊断，或用于测量疾病活动的程度。我们已经证明了这种方法是有效的，最近发现了一种生物标志物，可以预测四种不同情况的结果，包括炎症性肠病（克罗恩病和溃疡性结肠炎）、狼疮和血管炎——现在正在进入临床试验。拟议的项目将完成对过去十年中在这四个患者组中建立的一项大型研究的分析，并在未来五年内继续和扩展该研究，允许使用最新的技术进步并纳入其他疾病，如AIH、EGPA/Churg Strauss和多发性硬化症。

Between 5 and 10% of the population will develop an autoimmune or inflammatory disease at some point during their lifetime. These diseases behave differently from person to person, with some people having an aggressive course while others have a more benign disease. When such diseases develop doctors need to treat them "blind" - as they have no way of predicting which patients have naturally benign disease, requiring only minimal treatment, and those who will require more intensive treatment to obtain control. This is a major problem for patients and for the healthcare system. It means that patients who need intensive therapy often find that this needs to be delayed until their disease progresses and the need for such therapy becomes obvious. Conversely, the early indiscriminate use of treatment for these diseases may mean that those who would do well without such treatment receive it unnecessarily, exposing them to significant side-effects. Such poorly targeted use of treatments also wastes limited NHS resources.We will use cutting-edge "genomic" technology to measure the genes expressed in blood white cells in patients with a number of diseases before and after treatment. Analysing this gene expression data using advanced computational techniques will allow us to identify subsets of patients that would not be apparent using conventional clinical assessment, and to determine if these subsets are associated with different disease outcomes. Additional tests which can be developed based on these observations might allow early diagnosis of patients with rare diseases, or be used to measure the degree of disease activity. We have proven that such an approach works, having recently discovered a biomarker that predicts outcome in four different conditions, including inflammatory bowel disease (Crohn's disease and ulcerative colitis), lupus and vasculitis - this is now entering clinical trials.The proposed programme will complete the analysis of a large study established in these four patient groups over the last ten years, and continue and extend the study over the next five years, allowing the use of recent advances in technology and the inclusion of additional diseases, such as AIH, EGPA/Churg Strauss and multiple sclerosis.