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A BIOMARKER AND PATHWAY DISCOVERY PROGRAMME IN INFLAMMATORY DISEASE

炎症性疾病的生物标志物和通路发现计划

基本信息

批准号：
MR/L019027/1
负责人：
Kenneth Smith
金额：
$ 243.85万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FL019027%2F1
关键词：
BIOMARKER PATHWAY DISCOVERY PROGRAMME INFLAMMATORY

项目摘要

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.

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，一些人有侵袭性的病程，而另一些人则有更良性的疾病。当这种疾病发展时，医生需要对它们进行“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，以及哪些患者需要更密集的治疗才能获得控制。这对患者和医疗保健系统来说都是一个重大问题。这意味着需要强化治疗的患者往往发现这需要推迟，直到他们的疾病进展，对这种治疗的需求变得明显。相反，早期不分青红皂白地使用这些疾病的治疗可能意味着那些没有这种治疗就可以做得很好的人得到了不必要的治疗，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”技术来检测一些疾病患者在治疗前后血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传统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。根据这些观察结果开发的额外测试可能会让罕见疾病的患者得到早期诊断，或者被用来衡量疾病活动的程度。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记物，可以预测四种不同情况下的结果，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。拟议的计划将完成对过去十年在这四个患者组建立的大型研究的分析，并在未来五年继续和延长研究，允许使用最新的技术进步和包括其他疾病，如AIH，EGPA/Churg Strauss和多发性硬化症。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Peripheral Immune Cell Populations Associated with Cognitive Deficits and Negative Symptoms of Treatment-Resistant Schizophrenia.

DOI：
10.1371/journal.pone.0155631
发表时间：
2016
期刊：
PloS one
影响因子：
3.7
作者：
Fernandez-Egea E;Vértes PE;Flint SM;Turner L;Mustafa S;Hatton A;Smith KG;Lyons PA;Bullmore ET
通讯作者：
Bullmore ET

Leucocyte subset-specific type 1 interferon signatures in SLE and other immune-mediated diseases.

DOI：
10.1136/rmdopen-2015-000183
发表时间：
2016
期刊：
RMD open
影响因子：
6.2
作者：
Flint SM;Jovanovic V;Teo BW;Mak A;Thumboo J;McKinney EF;Lee JC;MacAry P;Kemeny DM;Jayne DR;Fong KY;Lyons PA;Smith KG
通讯作者：
Smith KG

A blood-based prognostic biomarker in inflammatory bowel disease

炎症性肠病的血液预后生物标志物