Vasculitis and Translational Medicine

National Institute Of Arthritis And Musculoskeletal And Skin Diseases

Investigators

Linked publications, trials & patents

Abstract

Recruitment to date remains strong within the Vasculitis Natural History Study but was limited due to the pandemic. 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 more than 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 (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 further on the role of qualitative and quantitative metrics to assess 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. 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 approximately 100 patients with a confirmed diagnosis of RP. 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 have published two papers detailing discovery of a new disease called the VEXAS (vacuole, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. VEXAS is due to somatic mutations in UBA1 in blood in male patients with adult-onset inflammatory diseases. The condition is hiding out among various forms of vasculitis, including relapsing polychondritis, giant cell arteritis, and polyarteritis nodosa. We are working to define treatment options for this frequently fatal disease, including development 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. Survey work is being conducted in collaboration with the Vasculitis Patient Powered Research Network (VPPRN). Mechanistic work is being conducted under a collaborative initiative at the Intramural NIH Program led by Dr. Mariana Kaplan.