Coordination Funds

协调基金

• 批准号: 418294985
• 负责人: Professor Dr. Gerhard Krönke
• 金额: --
• 依托单位: Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie (einschließlich Arbeitsbereich Physikalische Medizin)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418294985?language=en
• 关键词: Coordination; Funds

Rheumatoid Arthritis (RA) is a severe chronic inflammatory disease that is characterized by an early breach in immune tolerance and persisting autoimmunity. The autoimmune response triggers the onset of a chronic arthritis affecting peripheral joints, which typically show synovial inflammation and destruction of articular cartilage and bone. Research in the field of RA has been traditionally focused on the understanding of the mechanisms underlying synovitis and joint destruction. These efforts resulted in the successful development of targeted immune modulatory drugs for the treatment of this disease. However, key questions about factors responsible for the breach in immune tolerance and the initial onset of disease remain unanswered. As a consequence, current therapies primarily aim to suppress the inflammatory response, rather than targeting autoimmunity, inducing tolerance or offering preventive strategies. Although usually effective in controlling disease activity to some extent, the established treatments do not tackle the underlying problem of autoimmunity and thus require a life-long treatment. Curative therapeutic concepts for RA patients are still out of reach. Within the Research Unit named PANDORA (Pathways triggering autoimmunity and defining onset of early rheumatoid arthritis), we bundle the expertise of internationally-renowned scientists and seek to unravel the mechanisms responsible for the early immune-pathogenesis of RA. By focusing on two key checkpoints - the loss of immune tolerance and the transition from autoimmunity to inflammation - we want to identify new concepts underlying the pathogenesis of early RA and thereby develop strategies for preventive and curative treatment approaches. Embedding this Research Unit into the research environment and infrastructure of the Friedrich Alexander University Erlangen-Nürnberg (FAU) and the University Hospital of Erlangen (UKER) offers the unique possibility of combining cutting edge techniques in immunology and molecular biology with preclinical disease models, modern imaging and well-characterized RA patient cohorts. Together with one ongoing and one additionally planned innovative clinical trial that seem to re-induce tolerance in RA, this concept provides the ground for a high level translational research program.

类风湿性关节炎（RA）是一种严重的慢性炎症性疾病，其特征是免疫耐受的早期破坏和持续的自身免疫。自身免疫反应触发慢性关节炎的发作，影响外周关节，其通常显示滑膜炎症和关节软骨和骨的破坏。RA领域的研究传统上集中于对滑膜炎和关节破坏的潜在机制的理解。这些努力导致成功开发用于治疗这种疾病的靶向免疫调节药物。然而，有关免疫耐受性破坏和疾病最初发作的因素的关键问题仍然没有答案。因此，目前的治疗主要旨在抑制炎症反应，而不是靶向自身免疫，诱导耐受或提供预防策略。虽然通常在一定程度上有效地控制疾病活动，但已建立的治疗方法不能解决自身免疫的根本问题，因此需要终身治疗。RA患者的治愈性治疗概念仍然遥不可及。在名为PANDORA（触发自身免疫和定义早期类风湿性关节炎发作的途径）的研究单位内，我们将国际知名科学家的专业知识结合起来，并寻求解开RA早期免疫发病机制的机制。通过关注两个关键检查点--免疫耐受的丧失和从自身免疫向炎症的转变--我们希望确定早期RA发病机制的新概念，从而制定预防性和治愈性治疗方法的策略。将该研究单位嵌入到弗里德里希亚历山大大学埃尔朗根-纽伦堡（FAU）和埃尔兰根大学医院（UKER）的研究环境和基础设施中，提供了将免疫学和分子生物学的尖端技术与临床前疾病模型，现代成像和良好表征的RA患者队列相结合的独特可能性。再加上一个正在进行的和一个额外计划的创新临床试验，似乎重新诱导RA的耐受性，这一概念提供了一个高水平的转化研究计划的基础。