Central Clinical Infrastructure (Z1-Project)

转化研究需要持续接触患者和匹配的对照，以获得标本和（临床）表型。对罕见病患者的救助自然是有限的。为了克服转化/临床研究的这一障碍，CRU建立了核心单位中央临床基础设施（Z1-Project）。z1项目系统地收集PD标本和匹配对照。此外，它最详尽的表型PD患者。样品采集和表型分型均按照sop进行，由Z1-项目在第一个FP期间开发和不断完善。此外，只要有可能，Z1-Project会对PD患者进行纵向随访，包括对个体患者进行重复采样和表型分型。表型包括详细的临床检查，病史和分析实验室参数。所有数据均在CRU数据库中编译，该数据库由Z1-Project在第一次FP期间安装，并由Z2-Project -生物统计学和系统医学持续分析。这些PD患者的表型组学是解释来自患者标本的不同结果及其精确临床背景的关键，也是通过剖析PD患者临床表型中典型的个体间异质性来阐明PD发病机制的关键。在第二个FP中，Z1-Project将继续为CRU项目提供所需的所有标本，并进一步系统地对PD患者进行表型分析，增加CRU数据库中PD患者资料的编制数量。一个新的中心方面的表型将是一个深入的神经分析大疱性类天疱疮（BP）患者。这种神经学分析将被添加到表型分析中，因为近年来，越来越多的证据表明，多种中枢神经系统疾病先于BP，甚至可能引发BP的出现。为了解决这个问题，将对BP患者进行临床和神经心理学检查，并使用基于mri的技术对其中枢神经系统进行成像，绘制其形态和功能。因此，CRU将能够确定BP患者是否典型地患有至少亚临床神经功能缺陷，以及这些缺陷是否具有共同的形态或功能特征。z1项目还将组织完成BP患者亚队列的多组学分析，包括外周血转录组学、代谢组学和蛋白质组学（特别是细胞因子和趋化因子水平），从急性发作开始，为期6个月。这些组学将成为z2项目中trans-ome-wide association study （trans- OWAS）的一部分，旨在建立个体通路活性与疾病之间的因果关系，从而揭示特定分子通路的致病意义。此外，这些多组学将使z2项目中多变量生物标志物的开发成为可能。

Translational research requires continuous access to patients and matched controls to obtain specimens and (clinical) phenotypes. The access to patients suffering from rare diseases is naturally limited. To overcome this obstacle for its translational/clinical research, the CRU established the core unit Central clinical Infrastructure (Z1-Project). The Z1-Project systematically collects specimens of PD and matched controls. Furthermore, it most exhaustively phenotypes PD patients. Both the sample collection and the phenotyping is conducted according to SOPs, developed and continuously refined by the Z1- Project during the 1st FP. Also, wherever possible, the Z1-Project longitudinally follows-up PD patients, which includes repeated sampling and phenotyping of individual patients. The phenotyping includes a detailed clinical examination, history, and profiling laboratory parameters. All data are compiled in the CRU database, which was installed by the Z1-Project during the 1st FP, and is continuously analyzed by the Z2-Project - Biostatistics and Systems Medicine. These compiled phenomics of PD patients are key to interpret the different results, derived from the patients’ specimens, with respect to their precise clinical context and to elucidate the pathogenesis of PDs by dissecting the typical interindividual heterogeneity in the clinical phenotype of PD patients. In the 2nd FP, the Z1-Project will continue to provide all specimens required for the CRU projects and to further systematically phenotype PD patients and increase the number of PD patient profiles compiled in the CRU database. A new central aspect of the phenotyping will be an in-depth neurological profiling of bullous pemphigoid (BP) patients. This neurological profiling will be added to the phenotyping because in recent years, evidence has accumulated that diverse disorders of the CNS precede BP and may even initiate its emergence. To address this, BP patients will be clinically and neuropsychologically examined and their CNS will be imaged using MRI-based technologies mapping its morphology and functionality. Hereby, the CRU will be able to determine whether BP patients typically suffer from at least subclinical neurological deficits and whether these deficits have common morphological or functional features. The Z1-Project will also organize the completion of a multi-omics profile of a subcohort of our BP patients, which will include peripheral transcriptomics, metabolomics, and proteomics (specifically cytokine and chemokine levels) through the course of 6 months starting with an acute flare of disease. These Omics will be part of a trans-ome-wide association study (trans- OWAS) performed in the Z2-Project to establish cause-effect relationships between the activity of individual pathways and disease, thus revealing the pathogenic significance of specific molecular pathways. Furthermore, these multi-omics will enable the development of multivariate biomarkers in the Z2-Project.