Sjögren’s Team for Accelerating Medicines Partnership (STAMP)

摘要 舍格伦病（Sjögren's Disease，SjD）是一种常见的全身性自身免疫性疾病， 风湿性疾病的患病率仅次于类风湿性关节炎。它主要影响唾液和泪腺 腺体通过淋巴细胞浸润和自身抗体介导的炎症，导致显着 发病率。大约三分之一的SjD患者有腺体外受累， 淋巴瘤风险增加不幸的是，在解决许多未得到满足的问题方面进展有限， 在SJD的需要。确诊是多学科的性质，往往会导致显着的延误。很少 除了症状管理之外，还有其他治疗选择，最近的临床试验结果已经被证实。 失望因此，更好地了解疾病的发病机制是至关重要的， 使用拆除和重建方法来实现。这一目标的核心是， SjD患者的特征。多学科的Sjögren团队加速药物合作伙伴关系 （STAMP）是集合这一资源的理想平台。该团队的专业知识包括以自身免疫为重点的 分子生物学、遗传学和流行病学/临床研究，以及在建立 大型队列的参与者与存储的生物标本和精致详细的表型表征。 除了招募新的参与者，现有的队列将提供独特的机会， 对先前评估的SjD参与者进行10至15年随访。我们建议的疾病小组（DT）是 战略定位，以应用尖端技术来询问组织和系统 SjD的生物学，以确定治疗途径和靶点，目标如下：1）计划阶段： 合作制定5年科学研究议程和SjD患者表型分型SOP 与其他AMP DT以及技术和分析核心（TAC）一起使用。设计标准化协议， 招募、入组、收集生物标本并对SjD观察队列进行深入表型分析， 对照确定SjD的研究重点，以更好地了解分子和表型异质性 2）中试阶段：校准临床评估， 在招聘地点对采购进行抽样，并评估SOP。我们将与其他部门密切合作， 和TAC，以a）最终确定SOP并在所有地点实施; B）利用我们的多学科专业知识， 通过对分子和临床数据的初步分析，启动SjD的解构-重建; 3） 规模扩大阶段：增加参与者招募并与TAC合作， 重建SjD。跨研究中心实施的标准化方案将使STAMP能够询问 SjD的组织和系统生物学使用深度测序和其他尖端技术，以更好地 了解1）SjD的发病机制，并确定治疗靶点和新的生物标志物;和2）疾病 SjD从非SjD发展为SjD以及从“早期SjD”发展为“晚期SjD”的固有机制。

ABSTRACT Sjögren’s Disease (SjD, formerly known as Sjögren’s syndrome) is a common systemic autoimmune rheumatic disorder second only to rheumatoid arthritis in prevalence. It primarily affects salivary and lacrimal glands through lymphocytic infiltration and autoantibody-mediated inflammation, resulting in significant morbidity. Approximately one third of SjD patients have extraglandular involvement and have a remarkably elevated risk for lymphoma. Unfortunately, limited progress has been made in addressing the many unmet needs in SjD. Confirmatory diagnosis is multidisciplinary in nature and often results in significant delay. Scant therapeutic options exist outside of symptom management, and results from recent clinical trials have been disappointing. Thus, a better understanding of the pathogenetic mechanisms of disease is critical, and can be achieved using a de- and re-construction approach. Central to this goal, is the need for deeply characterized patients with SjD. The multidisciplinary Sjögren’s Team for Accelerating Medicines Partnership (STAMP) is ideally poised to assemble this resource. The team’s expertise includes autoimmunity-focused molecular biology, genetic, and epidemiologic/clinical research, and a remarkable track-record in establishing large cohorts of participants with stored biospecimens and exquisitely detailed phenotypic characterization. In addition to recruiting new participants, the existing cohorts will provide the unique opportunity to perform 10 to 15-year follow-up of previously evaluated SjD participants. Our proposed Disease Team (DT) is strategically positioned to apply cutting-edge technologies to interrogate the tissue and systems biology of SjD to identify therapeutic pathways and targets, with the following aims: 1) Planning Phase: Develop a 5-year scientific research agenda and SOPs for phenotyping SjD patients in collaboration with other AMP DTs and Technology and Analytics Cores (TACs). Design standardized protocols to recruit, enroll, collect biospecimens and perform deep phenotyping of observational cohorts of SjD and controls. Identify research priorities for SjD to better understand the molecular and phenotypic heterogeneity and natural history at both tissue and cell levels; 2) Pilot Phase: Calibrate clinical assessments and sample procurement across recruitment sites and evaluate SOPs. We will work closely with other DTs and TACs to a) finalize SOPs and implement them at all sites; b) leverage our multidisciplinary expertise to initiate the deconstruction-reconstruction of SjD via preliminary analyses of molecular and clinical data; 3) Scale up Phase: Increase participant recruitment and work with TAC to molecularly deconstruct and reconstruct SjD. Standardized protocols implemented across sites will enable STAMP to interrogate the tissue and systems biology of SjD using deep sequencing and other cutting-edge technologies, to better understand 1) the pathogenesis of SjD and identify therapeutic targets, and new biomarkers; and 2) disease mechanisms inherent to progression of SjD from non-SjD to SjD, and from “early SjD” to “advanced SjD”.