Coordination Funds

类风湿性关节炎(RA)是一种严重的慢性炎症性疾病，其特征是早期免疫耐受被破坏，并持续自身免疫。自身免疫反应触发慢性关节炎的发作，影响周围关节，通常表现为滑膜炎症和关节软骨和骨的破坏。传统上，类风湿关节炎领域的研究主要集中在了解滑膜炎和关节破坏的机制上。这些努力导致了治疗这种疾病的定向免疫调节药物的成功开发。然而，关于免疫耐受被打破的原因以及疾病最初发病的关键问题仍然没有得到回答。因此，目前的治疗主要旨在抑制炎症反应，而不是针对自身免疫、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，但现有的治疗方法并不能解决自身免疫的根本问题，因此需要终生治疗。治疗类风湿性关节炎患者的治疗理念仍然遥不可及。在名为Pandora(触发自身免疫和定义早期类风湿性关节炎发病的途径)的研究单位内，我们汇集了国际知名科学家的专业知识，并试图揭示导致RA早期免疫发病的机制。通过关注两个关键的检查点--免疫耐受性的丧失和从自身免疫到炎症的转变--我们希望确定早期类风湿关节炎发病机制的新概念，从而制定预防和治疗方法的策略。将该研究单元嵌入弗里德里希·亚历山大大学埃尔兰根-纽伦堡分校(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、现代成像和具有良好特征的RA患者队列相结合的独特可能性。再加上一项正在进行的和另一项计划中的创新临床试验，似乎重新诱导了RA的耐受性，这一概念为高水平的转化性研究计划提供了基础。

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.