Vasculitis and Translational Medicine

到目前为止，血管炎自然史研究的招募仍然很强劲。所有在美国国立卫生研究院临床中心就诊的患者都接受全面的临床评估，并向不断增长的生物库提供样本。在过去的一年里，我们集中在两种形式的血管炎：大血管血管炎（LVV）和复发性多软骨炎（RP）。目前，我们已经根据一项观察性方案（14-AR-0200）评估了600名血管炎患者，除了对选定的患者进行长期随访外，每年还将继续观察约100名新患者。

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 year, we have focused on two forms of vasculitis: large vessel vasculitis (LVV) and relapsing polychondritis (RP). We have currently evaluated >600 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. 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 the complicated relationship between clinical assessment, laboratory assessment, and vascular imaging studies over time in patients with LVV. This work has informed ongoing efforts within the OMERACT community to develop standardized definitions of disease activity in LVV for use in clinical trials. We continue to refine qualitative and quantitative metrics of vascular inflammation by FDG-PET. One such metric that we developed and validated, PET Vascular Activity Score (PETVAS), is currently being used in ongoing international clinical trials in vasculitis as a novel outcome measure. We also have refined PET imaging protocols to optimize performance characteristics of PET to detect and monitor vascular activity. We published on the kinetics of FDG arterial uptake, demonstrating that delayed imaging approaches are preferable in LVV. We have also continued to use pattern of vascular involvement, as defined by angiography or FDG-PET, as a method to identify clinically meaningful subsets of patients with LVV. 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 have also firmly established a new research initiative in relapsing polychondritis. 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 started recruiting patients with RP to the NIH Clinical Center in August 2016. Since that time, we have evaluated >100 patients with a confirmed diagnosis of RP, with over 80 patients currently on the waiting list to be seen. 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. This year we have published a paper using latent class analysis to identify three clinical subsets of patients with RP. We anticipate these findings will create a framework to understand causal factors that underlie clinical heterogeneity in RP. Recently, our group participated in the discovery of a somatic mutation in hematologic progenitor cells that is causal for disease in 8% of patients with RP in the NIH cohort. This discovery raises exciting possibilities of the role of somatic mutations in adult-onset rheumatologic conditions and raises potential for novel therapeutic approaches, including bone marrow transplantation, in these diseases. We have begun to develop deep sequencing protocols to identify clonal hematopoiesis in patients with RP and other forms of vasculitis. 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. Survey work is being conducted in collaboration with the Vasculitis Patient Powered Research Network (VPPRN). Mechanistic work will be conducted under a collaborative initiative at the Intramural NIH Program led by Dr. Mariana Kaplan.