Vasculitis and Translational Medicine

血管炎和转化医学

• 批准号: 10925924
• 负责人: Peter Grayson
• 金额: $ 120.72万
• 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/10925924
• 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; Collaborations; Communication; Complex; Data; Data Collection; Dedications; 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; Molecular; Monitor; Morbidity - disease rate; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Natural History; Neck; North America; Nose; Organ; Oscillometry; Outcome; Pathogenesis; Patient Selection; Patients; Pattern; Physical Examination; Physicians; Positron-Emission Tomography; Prediction of Response to Therapy; Prognostic Factor; Protocols documentation; Publishing; Pulmonary function tests; Radiology Specialty; 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; 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 heterogeneity; disease natural history; epidemiology study; fluorodeoxyglucose positron emission tomography; genetic variant; imaging biomarker; indexing; inflammatory marker; molecular imaging; mortality; next generation sequencing; novel; novel marker; observational cohort study; pandemic disease; pandemic impact; patient advocacy group; patient oriented; patient subsets; personalized medicine; predict clinical outcome; prognostic value; programs; prospective; radiological imaging; randomized, clinical trials; recruit; research clinical testing; standard of care; therapeutic evaluation; translational medicine; translational research program; trend; trial design; vascular inflammation

Recruitment to date remains strong within the Vasculitis Natural History Study. 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 900 patients with vasculitis under an observational protocol (14-AR-0200) and continue to see approximately 50 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. We recently have reported 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 using next generation sequencing approaches to understand the molecular basis of disease and clinical heterogeneity. 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.

迄今为止，血管炎自然史研究的招募仍然强劲。在 NIH 临床中心就诊的所有患者都会接受全面的临床评估，并向不断扩大的生物库贡献样本。在过去的几年中，我们主要关注两种形式的血管炎：大血管血管炎（LVV）和复发性多软骨炎（RP）。 目前，我们已根据观察方案 (14-AR-0200) 对 900 多名血管炎患者进行了评估，并且除了随着时间的推移对选定的患者进行跟踪之外，每年还会继续观察约 50 名新患者。 自上次报告以来，我们继续发表有关血管成像作为大血管血管炎 (LVV) 疾病活动生物标志物的作用的文章。巨细胞动脉炎（GCA）和大动脉炎（TAK）是大血管炎（LVV）的两种主要形式，由主动脉和主分支的炎症定义。 对 LVV 疾病活动性的临床评估可能具有挑战性，从而对有效监测和治疗构成障碍。 LVV 患者在炎症标志物正常的明显持续临床缓解期间可能会出现新的血管病变。 虽然一些研究已经检验了分子成像在 LVV 中的潜力，但 FDG-PET 在检测血管炎症、随时间监测疾病活动和预测临床结果方面的作用仍不清楚。我们最近报告了队列中的纵向数据，以显示血管炎症随时间变化的趋势，并研究 FDG-PET 检测到的血管炎症是否具有预后价值。我们提供了世界上仅有的一些关于 PET 扫描结果与未来疾病进展关系的数据。我们小组的工作继续制定 LVV 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效果，并向研究人员通报疾病的自然史。 我们还在一项前瞻性观察队列研究中继续研究复发性多软骨炎。复发性多软骨炎是一种多系统风湿病，其特征是软骨结构炎症，包括耳、鼻、关节和气道。 目前尚无针对 RP 的诊断测试，器官受累情况各异，诊断依赖于对临床特征模式的识别，而这些特征有时可能非常微妙。 RP 对死亡率和发病率有很大影响，器官损伤和由此导致的残疾率很高。 气道受累会使 RP 患者无法沟通、呼吸困难，并依赖气管切开术生存。 过去五年来，我们在 NIH 临床中心对 100 多名 RP 患者进行了评估。 所有患者均接受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、直接喉镜检查、示波法肺功能测试以及颈部磁共振成像。 此外，我们开发了一种新颖的方法来进行胸部动态计算机断层扫描（CT），作为检测大气道结构损伤的非侵入性方法。 我们预计，随着我们开始前瞻性地描述这种复杂、异质的疾病，该队列将在未来几年成为丰富的临床信息来源。 除了对 RP 进行临床分析外，我们还收集并储存生物样本以用于未来的机制研究。 去年，我们继续定义了一种在我们的队列中发现的新疾病，称为 VEXAS（液泡、E1 酶、X 连锁、自身炎症、体细胞）综合征。 VEXAS 是由患有危及生命的多系统疾病的成年患者骨髓中 UBA1 体细胞突变引起的。我们最近确定了生存的预后因素以及这些关联的机制基础。 我们正在使用下一代测序方法来了解疾病和临床异质性的分子基础。我们正在努力确定这种常见致命疾病的治疗方案，包括与我们的血液学同事合作在 NIH 实施骨髓移植方案。 我们正在帮助领导全球努力从临床表现、诊断算法、治疗和流行病学研究方面定义这种新疾病。 最后，鉴于当前的大流行，我们正在参与旨在评估 COVID-19 对血管炎等自身免疫性疾病患者影响的研究。 这些工作包括以患者为基础的调查，旨在评估大流行对血管炎患者健康相关行为和结果的影响，以及机制研究，以确定暴露于 SARS-COV-2 的血管炎患者的免疫反应。机械工作是在玛丽安娜·卡普兰博士领导的 NIH 校内项目的一项合作倡议下进行的。

项目成果

Stenosis and Pseudostenosis of the Upper Extremity Arteries in Large-Vessel Vasculitis.

大血管血管炎中上肢动脉的狭窄和假性狭窄。

• DOI: 10.1002/acr2.1018
• 发表时间: 2019
• 期刊: ACR open rheumatology
• 影响因子: 3.4
• 作者: Marinelli,KathleenC;Ahlman,MarkA;Quinn,KaitlinA;Malayeri,AshkanA;Evers,Robert;Grayson,PeterC
• 通讯作者: Grayson,PeterC

Vascular calcification in patients with large-vessel vasculitis compared to patients with hyperlipidemia.

• DOI: 10.1016/j.semarthrit.2018.09.001
• 发表时间: 2019-06
• 期刊: Seminars in arthritis and rheumatism
• 影响因子: 5
• 作者: Banerjee S;Bagheri M;Sandfort V;Ahlman MA;Malayeri AA;Bluemke DA;Yao J;Grayson PC
• 通讯作者: Grayson PC

Utility of the Brief Illness Perception Questionnaire to Monitor Patient Beliefs in Systemic Vasculitis.

简短疾病认知问卷在监测系统性脉管炎患者信念方面的实用性

• DOI: 10.3899/jrheum.190828
• 发表时间: 2020-12-01
• 期刊: The Journal of rheumatology
• 作者: Schwartz MN;Rimland CA;Quinn KA;Ferrada MA;Gribbons KB;Rosenblum JS;Goodspeed W;Novakovich E;Grayson PC
• 通讯作者: Grayson PC

Reply: On Semiquantitative Methods for Assessing Vascular 18F-FDG PET Activity in Large-Vessel Vasculitis.

答复：关于评估大血管血管炎中血管 18F-FDG PET 活性的半定量方法。

• DOI: 10.2967/jnumed.121.263158
• 发表时间: 2022
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Ahlman,MarkA;Maass-Moreno,Roberto;Grayson,PeterC
• 通讯作者: Grayson,PeterC

Reply.

回复。

• DOI: 10.1002/art.40923
• 发表时间: 2019
• 期刊: Arthritis & rheumatology (Hoboken, N.J.)
• 作者: Kim,AlfredHJ;Strand,Vibeke;Atkinson,JohnP
• 通讯作者: Atkinson,JohnP