AIM-for-RA

类风湿性关节炎(RA)影响大约1%的人口，其特点是 炎症和关节损伤，通常导致早期和早期的相当大的残疾和疼痛 既定的阶段。该领域未得到满足的主要需求领域包括：1)高度异质性和 不可预测的病程，2)罕见的持久缓解，3)现有治疗失败 在许多患者中实现较低的疾病活动性和/或限制进行性关节损害，以及4)缺乏 强健的生物标记物是个性化适当治疗策略所必需的。我们建议 滑膜组织中的细胞和分子变异是这种异质性和理解的基础 为提高病程预测的准确性和及时性提供理论依据。 选择具有较高持续RA控制率的精确治疗策略。穿过 持续协作的全球团队科学，AIM-for-RA团队已经开发出 解构RA滑膜活检组织的ART方案-这是一项深刻地 在RA发病机制中涉及的细胞和途径方面的高级知识，确定了新的治疗方法 目标，确定了疾病生物标志物，并在疾病预防方面开辟了新的机会。然而， 目前尚不清楚滑膜中的分子相互作用如何与已定义的 临床结果，从高危临床前期到关节炎发作，再到滑膜炎 结果。因此，AIM-for-RA疾病小组(DT)的目标是将与疾病相关的滑膜细胞 环境暴露、疾病结局和治疗的途径和动态串扰 反应，从而重建了疾病的发病轨迹。在DMARD-天真的RA杂交中- 基于节段性滑膜活检的9个部位50例类风湿关节炎患者的研究 集成技术，AIM 1将提供高质量的多模式临床表型和组织学 数据，以及滑膜组织和其他生物样本，以评估滑膜细胞和分子 途径与疾病的发生有关。对这些患者进行纵向随访和重复活检 在甲氨蝶呤单一治疗后，目标2将解决滑膜信号和多模式 数据预测早期未接受治疗的患者的甲氨蝶呤一线反应或失败 疾病。最后，在目标3中，在甲氨蝶呤反应不足的患者中，我们将解决是否 独特的滑膜细胞或分子特征直接预示着对生物治疗的阳性反应 瞄准这些功能。这一计划的成果将有可能迅速转化为 应用于改善RA疾病所有阶段的治疗结果。总体而言，协作、 全球AIM-for-RA团队对RA疾病的发病机制进行了开创性的观察 非常适合为关键问题提供信息，并满足领域中未得到满足的主要需求。

Rheumatoid arthritis (RA) affects approximately 1% of the population and is characterized by inflammation and joint damage, often leading to considerable disability and pain in both early and established stages. Key areas of unmet need in the field include the: 1) highly heterogeneous and unpredictable disease course, 2) rarity of lasting remissions, 3) failure of currently available treatments to achieve low disease activity and/or limit progressive joint damage in many patients, and 4) lack of robust biomarkers necessary to personalize appropriate treatment strategies. We propose that cellular and molecular variation in synovial tissue underlies this heterogeneity and that understanding the basis for this will improve the prediction of disease course and provide a rationale for the timely selection of precision treatment strategies with higher rates of sustained RA control. Through sustained collaborative global team-science, the AIM-for-RA Team has already developed state-of- the-art protocols that deconstructed RA synovial biopsy tissues - an innovation that profoundly advanced knowledge in cells and pathways involved in RA pathogenesis, identified novel treatment targets, identified disease biomarkers, and opened new opportunities in disease prevention. However, it remains unclear how molecular interactions in the synovium relate to the evolution of defined clinical outcomes, from the at-risk preclinical period to arthritis onset, and then through to synovitis outcome. Therefore, AIM-for-RA Disease Team (DT) aims to relate disease-relevant synovial cellular pathways and dynamic crosstalk to environmental exposures, disease outcomes and treatment response, thereby reconstructing the disease pathogenesis trajectory. In a DMARD-naïve RA cross- sectional synovial biopsy-based study of 50 RA patients across 9 sites using harmonized protocols and integrated technologies, Aim 1 will deliver high-quality multimodal clinical phenotype and histology data, along with synovial tissue and other biosamples, to evaluate how synovial cellular and molecular pathways relate to disease onset. With longitudinal follow-up and repeat biopsy of these individuals after methotrexate monotherapy, Aim 2 will address whether synovial signatures and multi-modal data predict first-line methotrexate response, or failure in patients with early previously untreated disease. Finally, in Aim 3, in patients with methotrexate inadequate response we will address whether distinct synovial cellular or molecular features predict a positive response to biologic therapies directly targeting these features. The outcomes of this program will have potential for rapid translational application to improve treatment outcomes at all RA disease stages. Collectively, the collaborative, global AIM-for-RA Team that has made seminal observations regarding RA disease pathogenesis is ideally suited to inform the key questions and meet major unmet needs in the field.