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或炎症性疾病。这些疾病的表现因人而异，有些人有一个积极的过程，而其他人有一个更良性的疾病。当这些疾病发展时，医生需要“盲目”治疗-因为他们无法预测哪些患者患有自然良性疾病，只需要最低限度的治疗，以及那些需要更密集治疗才能获得控制的患者。这对患者和医疗保健系统来说都是一个大问题。这意味着需要强化治疗的患者通常会发现，这需要推迟，直到他们的疾病进展和对这种治疗的需要变得明显。相反，早期对这些疾病不加区别地使用治疗方法可能意味着，那些不需要这种治疗就能活得很好的人接受了不必要的治疗，使他们面临严重的副作用。这种针对性不强的治疗方法也浪费了有限的NHS资源，我们将使用尖端的“基因组”技术，测量多种疾病患者治疗前后血白色细胞中表达的基因。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子集，并确定这些子集是否与不同的疾病结局相关。基于这些观察结果可以开发的其他测试可能允许早期诊断罕见疾病患者，或用于测量疾病活动程度。我们已经证明这种方法是有效的，最近发现了一种生物标志物，可以预测包括炎症性肠病在内的四种不同疾病的结果。（克罗恩病和溃疡性结肠炎），狼疮和血管炎-这是现在进入临床试验。拟议的方案将完成一个大型研究的分析，建立在这四个病人群体在过去十年，并在未来五年内继续和扩展这项研究，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.