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

免疫介导性炎症性疾病(IMID)是一种常见的疾病，会导致严重的疼痛、痛苦、功能丧失和过早死亡。它们在临床上是不同的，例如，通过不同的靶向皮肤、关节或肾脏，但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)、牛皮癣、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变。自20世纪90年代以来，生物药物和改进的治疗策略使相当大一部分IMID患者的治疗发生了革命性变化。然而，一些IMID并没有真正取得进展，即使在进步显著的情况下，许多患者对治疗还没有反应，或者随着时间的推移失去了反应--这是终生不治之症。因此，IMID领域仍然有很大的临床需求没有得到满足。一个令人兴奋的改善结果的方法是应用精确医学的原则，即患者将在正确的时间以正确的剂量接受正确的药物，而发生重大毒性的可能性最小。将精确医学引入IMID将需要将临床信息与复杂的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中出现的血液和受损组织中生成。从理论上讲，通过将这些信息整合在一起，我们可以创建患者的“分子图谱”，从而做出非常精确的治疗决定，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收集的此类数据只针对一种疾病，导致对更广泛的炎症医学领域的方法相当狭窄。这项提议将把许多英国生物库和临床队列数据集整合到一个可搜索和分析的实体中，由一个名为IMIDBio-UK的财团领导和协调，从而彻底改变这种情况。IMID Bio-UK将产生一条虚拟信息高速公路，使人们能够史无前例地访问整个英国关于IMID的信息。IMID-Bio-UK财团的愿景是利用丰富的生物样本储备、深度表型临床队列以及由一组非常成功的国家分层医学计划形成的高质量多组学数据的力量。这些资源将向研究人员提供，用于研究IMID生物学和预测药物反应，使用分子标记(生物标记)来定义疾病进展和药物作用的共同和独特机制(内型)。这将使生物制剂和新药在IMID范围内得到更广泛、更安全的使用。通过收集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，并为罕见或特征不佳的IMID的生物使用提供亟需的见解，最终为患者带来好处并节省医疗费用。

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.