MICA: Immune-Mediated Inflammatory Disease Biobanks in the UK (IMIDBio-UK)

免疫介导的炎症性疾病（IMID）是常见的医疗条件，导致严重的疼痛，痛苦，功能丧失和早期死亡。它们在临床上是多样的，例如通过不同地靶向皮肤、关节或肾脏，但具有一些共同的遗传特征、环境触发因素和炎症病理机制。IMID包括类风湿性关节炎（RA）、银屑病、系统性红斑狼疮（SLE）、干燥综合征、自身免疫性肝炎和原发性胆汁性肝硬化。自20世纪90年代以来，生物药物和改进的治疗策略已经彻底改变了相当一部分IMID患者的治疗。然而，一些IMID并没有真正取得进展，即使在那些进展显着的患者中，许多患者对治疗没有反应或随着时间的推移而失去反应-这是终身不可治愈的疾病。因此，在IMID领域仍有大量未满足的临床需求。一个令人兴奋的改善结果的方法是应用精准医学的原则，即患者将在正确的时间以正确的剂量接受正确的药物，同时具有显著毒性的机会最小。将精准医学引入IMID将需要将临床信息与复杂分子数据集整合在一起的大型数据集，这些数据集现在可以从IMID中发生的血液和受损组织中生成。从理论上讲，通过将这些信息放在一起，我们可以创建一个患者的“分子图谱”，从而可以做出非常精确的治疗决策，从而在降低风险的情况下带来更好的结果。然而，到目前为止，大多数IMID收集的此类数据仅针对一种疾病，导致对更广泛的炎症医学领域的相当狭窄的方法。该提案将彻底改变这种情况，将许多英国生物库和临床队列数据集汇集到一个可搜索和可分析的实体中，由一个名为IMIDBio-UK的联盟领导和协调。IMIDBio-UK将产生一个虚拟的信息高速公路，这将允许前所未有的访问有关IMID的信息在英国。IMID-Bio-UK联盟的愿景是利用丰富的生物样本储备的力量，深入的表型临床队列，以及从一组非常成功的国家分层医学计划形成的高质量的多组学数据。这些资源将提供给研究人员研究IMID生物学和预测药物反应，使用分子标志物（生物标志物）来定义疾病进展和药物作用的常见和独特机制（内型）。这将使生物制剂和新药在整个IMID范围内得到更广泛、更安全的使用。通过汇集IMID样本并比较数据和临床实践，我们将优化常见IMID的临床路径，并提供对罕见或特征不佳的IMID的生物学使用的迫切需要的见解，最终为患者带来益处并节省医疗保健费用。

Immune-mediated inflammatory diseases (IMIDs) are common medical conditions that cause substantial pain, distress, loss of function and early death. They are clinically diverse e.g. by variously targeting the skin, joints, or kidneys, but share some common genetic features, environmental triggers and inflammatory pathologic mechanisms. The IMIDs include rheumatoid arthritis (RA), psoriasis, systemic lupus erythematosus (SLE), Sjogren's syndrome, autoimmune hepatitis and primary biliary cirrhosis. Since the 1990s, biologic drugs and improved treatment strategies have revolutionised the treatment of a significant proportion of people with some IMIDs. However some IMIDs have not really progressed and even in those in which advances are notable, many patients do not yet respond to treatment or lose their responses over time - this in life long incurable diseases. Therefore, there remains great unmet clinical need in the IMID field.One exciting approach to improving outcomes is to apply the principles of precision medicine whereby patients will receive the 'right drug at the right time at the right dose' with minimal chance of having significant toxicity. Bringing precision medicine to IMIDs will require large datasets that integrate clinical information together with complex molecular datasets that can now be generated from the blood and damaged tissues that occur in IMIDs. In theory, by putting this information together we can create a 'molecular map' of a patient that allows very precise treatment decisions to be made that will bring better outcomes at reduced risk. Thus far however most IMID collections of such data have been specified for only one disease leading to a rather narrow approach to the broader inflammation medicine field. This proposal will revolutionise this scenario by bringing together many UK biobank and clinical cohort datasets into one single searchable and analysable entity, lead and coordinated by a consortium called IMIDBio-UK. IMIDBio-UK will generate a virtual information superhighway that will allow unprecedented access to information about IMIDs across the UK.The vision of the IMID-Bio-UK consortium is to harness the power of a rich reserve of biosamples, deeply phenotyped clinical cohorts, and high quality multi-omic data formed from a group of highly successful national stratified medicine programmes. These resources will be made available to researchers to study IMID biology and predict drug response, using molecular markers (biomarkers) to define common and unique mechanisms (endotypes) of disease progression and drug action. This will enable wider, safer use of biologics and new medicines across the IMID spectrum. By bringing together IMID samples and comparing data and clinical practice, we will optimise clinical pathways for common IMIDs, and provide much needed insight into biologic use in rarer or poorly characterised IMIDs, ultimately delivering patient benefit and health care savings.