Vasculitis and Translational Medicine

血管炎和转化医学

• 批准号: 10709760
• 负责人: Peter Grayson
• 金额: $ 161.45万
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10709760
• 关键词: ANCA vasculitis; Adult; Affect; Aortitis; Area; Arteries; Autoimmune Diseases; Biological Markers; Biological Specimen Banks; Blood Vessels; Bone Marrow; Bone Marrow Transplantation; COVID-19 impact; Chronic Disease; Classification; Clinical; Clinical Research; Clinical Trials; Clinical Trials Database; Clinical assessments; Cohort Studies; Collaborations; Complex; Data; Data Collection; Development; Diagnosis; Diagnostic tests; Disease; Disease Management; Disease Progression; Ear; Enzymes; Ethics; Etiology; Evaluation; Extramural Activities; Eye; Foundations; Future; Genetic; Germ-Line Mutation; Goals; Health behavior; Hearing Tests; Hematology; Image; Immune response; Immunologics; Inflammation; Intramural Research; Joints; Laboratories; Laryngoscopy; Lead; Lesion; Life; Light; Link; Magnetic Resonance Imaging; Methods; Monitor; Morbidity - disease rate; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Natural History; Neck; North America; Nose; Organ; Oscillometry; Outcome; Pathogenesis; Patients; Pattern; Physical Examination; Physicians; Positron-Emission Tomography; Prediction of Response to Therapy; Prognostic Factor; Protocols documentation; Publishing; Pulmonary function tests; Radiology Specialty; Randomized Clinical Trials; Recording of previous events; Relapse; Relapsing polychondritis; Reporting; Research; Research Design; Research Personnel; Rheumatism; Role; SARS-CoV-2 exposure; Sampling; Shapes; Skin; Somatic Mutation; Source; Steroids; Structure; Surveys; Syndrome; System; Systemic disease; Takayasu' s Arteritis; Temporal Arteritis; Time; Tissues; Tracheostomy procedure; Translational Research; Treatment Efficacy; United States National Institutes of Health; Vacuole; Vasculitis; Work; aged; autoinflammatory; base; behavioral outcome; biobank; biomarker development; biomarker discovery; cartilaginous; chest computed tomography; clinical care; clinical center; clinical heterogeneity; clinical outcome measures; clinical remission; cohort; data standards; design; diagnostic algorithm; disability; disease natural history; epidemiology study; fluorodeoxyglucose positron emission tomography; genetic variant; imaging biomarker; indexing; inflammatory marker; molecular imaging; mortality; novel; novel marker; pandemic disease; patient advocacy group; patient oriented; patient subsets; personalized medicine; predict clinical outcome; prognostic value; programs; prospective; radiological imaging; recruit; research clinical testing; standard of care; systemic autoimmunity; therapeutic evaluation; translational medicine; translational research program; trend; trial design; vascular inflammation

Recruitment to date remains strong within the Vasculitis Natural History Study despite challenges imposed by the ongoing pandemic. All patients seen at the NIH Clinical Center receive comprehensive clinical evaluation and contribute samples to a growing biobank. Over the last few years, we have mainly focused on two forms of vasculitis: large vessel vasculitis (LVV) and relapsing polychondritis (RP). We have currently evaluated more than 800 patients with vasculitis under an observational protocol (14-AR-0200) and continue to see approximately 100 new patients each year in addition to following selected patients over time. Since the last report, we continue to publish articles on the role of vascular imaging as a biomarker of disease activity in large-vessel vasculitis (LVV). Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are the two major forms of large-vessel vasculitis (LVV), defined by inflammation of the aorta and primary branches. Clinical assessment of disease activity in LVV can be challenging, thus posing a barrier to effective monitoring and treatment. Patients with LVV can develop new vascular lesions during periods of apparent sustained clinical remission with normal inflammatory markers. While several studies have examined the potential of molecular imaging in LVV, the role of FDG-PET to detect vascular inflammation, monitor disease activity over time, and predict clinical outcomes remains unclear. In the past year, we have reported on longitudinal data within the cohort to show trends in vascular inflammation over time and to investigate whether vascular inflammation detected by FDG-PET has prognostic value. We have provided some of the only data available in the world on the relationship of PET scan findings and future disease progression. Work from our group continues to shape standard of care for clinical disease activity assessment in LVV, to influence novel trial designs to test therapeutic efficacy, and to inform researchers about the natural history of the disease. We also continue to investigate relapsing polychondritis in a prospective observational cohort study. Relapsing polychondritis is a multisystem, rheumatologic disease characterized by inflammation of cartilaginous structures including the ear, nose, joints and airways. There are currently no diagnostic tests for RP, organ involvement is variable, and diagnosis is dependent on the identification of a pattern of clinical features that can be, at times, quite subtle. RP has a large impact on mortality and morbidity with a high rate of organ damage and resultant disability. Airway involvement can render patients with RP unable to communicate, struggling to breath, and dependent on a tracheostomy for survival. We have evaluated over 100 patients with RP at the NIH Clinical Center over the last five years. All patients undergo comprehensive disease-specific clinical assessment including a detailed history and physical examination, audiometry, direct laryngoscopy, pulmonary function tests with oscillometry, and magnetic resonance imaging of the neck. In addition, we developed a novel method to perform dynamic computed tomography (CT) of the chest as a non-invasive way to detect structural damage to large airways. We anticipate that this cohort will be a rich source of clinical information for years to come as we begin to prospectively characterize this complex, heterogeneous disease. In addition to clinically profiling RP, we collect and bank biospecimens for use in future mechanistic studies. Over the last year, we continue to define a new disease that was discovered in our cohort known as the VEXAS (vacuole, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. VEXAS is caused by somatic mutations in UBA1 in bone marrow in adult patients with life-threatening multisystem disease. We recently identified prognostic factors for survival and underlying the mechanistic basis for these associations. We are working to define treatment options for this frequently fatal disease, including implementation of a bone marrow transplantation protocol at the NIH in collaboration with our hematology colleagues. We are helping to lead worldwide efforts to define this new disease in terms of clinical manifestations, diagnostic algorithms, treatment, and epidemiologic studies. Finally, in light of the ongoing pandemic, we are participating in research designed to assess the impact of COVID-19 on patients with autoimmune diseases, including vasculitis. These efforts have included both patient-based surveys designed to assess the impact of the pandemic on health-related behavior and outcomes in patients with vasculitis as well as mechanistic studies to determine immune responses in patients with vasculitis who are exposed to SARS-COV-2. Mechanistic work is being conducted under a collaborative initiative at the Intramural NIH Program led by Dr. Mariana Kaplan.

尽管正在进行的大流行构成的挑战，但迄今为止迄今为止的招募仍然很强。在NIH临床中心看到的所有患者均接受全面的临床评估，并为不断增长的生物库贡献样本。在过去的几年中，我们主要集中在两种形式的血管炎上：大血管血管炎（LVV）和复发性多结膜炎（RP）。 我们目前已经根据观察方案（14-AR-0200）评估了800多名血管炎患者，除了随着时间的推移选择以下患者外，每年仍将看到大约100名新患者。 自上次报道以来，我们继续发表有关血管成像作为大周围血管炎（LVV）中疾病活性生物标志物的作用的文章。巨细胞动脉炎（GCA）和高山动脉炎（TAK）是大型血管炎（LVV）的两种主要形式，是由主动脉和原发性分支的炎症定义的。 LVV中疾病活动的临床评估可能具有挑战性，从而为有效的监测和治疗带来了障碍。 LVV患者可以在正常的炎症标志物和正常的临床临床缓解期间出现新的血管病变。 尽管几项研究检查了LVV中分子成像的潜力，但FDG-PET在检测血管炎症，随着时间的推移监测疾病活动以及预测临床结果的作用尚不清楚。在过去的一年中，我们已经报告了队列中的纵向数据，以显示随着时间的流逝，血管炎症的趋势，并研究FDG-PET检测到的血管炎症是否具有预后价值。我们提供了世界上唯一有关PET扫描发现与未来疾病进展的关系的数据。我们小组的工作继续塑造LVV中临床疾病活动评估的护理标准，影响新的试验设计以测试治疗功效，并将其告知研究人员有关疾病的自然史。 在一项前瞻性观察队列研究中，我们还继续研究复发性多发性炎。复发性多发性炎是一种多系统的风湿病疾病，其特征是软骨结构的炎症，包括耳朵，鼻子，关节和气道。 目前尚无针对RP的诊断测试，器官受累是可变的，并且诊断取决于识别临床特征模式的识别，这些模式有时可能很微妙。 RP对死亡率和发病率具有很大的影响，并具有高器官损伤和导致的残疾。 气道参与可以使RP患者无法交流，呼吸困难，并依赖于气管造口术以生存。 在过去的五年中，我们在NIH临床中心评估了100多名RP患者。 所有患者都接受了全面的疾病特异性临床评估，包括详细的病史和体格检查，听力测定法，直接喉镜检查，具有振荡的肺功能测试以及颈部的磁共振成像。 此外，我们开发了一种新颖的方法来执行胸部的动态计算机断层扫描（CT）作为一种非侵入性方法来检测对大型航空公司的结构损害。 我们预计，随着我们开始将这种复杂的，异质性疾病的特征来看，这一队列将是未来几年的丰富临床信息来源。 除了临床分析RP外，我们还收集和银行生物测量供以后的机械研究中使用。 在过去的一年中，我们继续定义一种新的疾病，该疾病是在我们的同类中被发现的，即Vexas（液泡，E1酶，X连锁，自身炎症，体细胞）综合征。 Vexas是由骨髓中UBA1的体细胞突变引起的，患有生命的多系统疾病。我们最近确定了这些关联的生存和基本基础的预后因素。 我们正在努力定义这种经常致命疾病的治疗选择，包括与我们的血液学同事合作实施NIH的骨髓移植方案。 我们正在帮助全球努力从临床表现，诊断算法，治疗和流行病学研究来定义这种新疾病。 最后，鉴于正在进行的大流行，我们正在参加研究，旨在评估Covid-19对包括血管炎在内的自身免疫性疾病患者的影响。 这些努力包括基于患者的调查，旨在评估大流行对血管炎患者的健康相关行为和结果的影响，以及确定暴露于SARS-COV-2的血管炎患者的免疫反应。机械工作是根据玛丽安娜·卡普兰（Mariana Kaplan）博士领导的壁内NIH计划的合作计划进行的。