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Principal Investigator: Peter Grayson
Organization: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
Fiscal Year: 2020
Award: $1,522,745
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
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.
Terms: <2019 novel coronavirus><2019-nCoV><21+ years old><ANCA><Adult><Adult Human><Affect><Angiitis><Angiogram><Angiography><Anti-Neutrophil Cytoplasmic Antibody><Antineutrophil Cytoplasmic Antibodies><Aortitis><Area><Arteries><Arteritis><Audiogram><Audiometric Test><Audiometry><Autoimmune Diseases><Biological Markers><Blood Vessels><Body Tissues><Bone Marrow Grafting><Bone Marrow Transplant><Bone Marrow Transplantation><Brachiocephalic Ischemia><COVID-19><COVID19><Causality><Characteristics><Chronic Disease><Chronic Illness><Classification><Clinical><Clinical Evaluation><Clinical Research><Clinical Study><Clinical Testing><Clinical Trials><Clinical Trials Database><Clinical assessments><Collaborations><Communities><Complex><Conventional X-Ray><Cranial Arteritis><Data><Data Collection><Development><Diagnosis><Diagnostic Radiology><Diagnostic X-Ray><Diagnostic X-Ray Radiology><Diagnostic radiologic examination><Diagnostic tests><Disease><Disease Management><Disorder><Disorder Management><EXTMR><Ear><Ethics><Etiology><Evaluation><Exposure to><Extramural><Extramural Activities><Eye><Eyeball><FDG PET><Foundations><Future><Gene variant><General Radiology><Genetic><Germ-Line Mutation><Germline Mutation><Giant Cell Arteritis><Goals><Health><Hearing Tests><Hematology><Hematopoiesis><Hematopoietic Cellular Control Mechanisms><Hereditary Mutation><History><Horton Disease><Horton Giant Cell Arteritis><Horton's Giant Cell Aortitis><Image><Immune response><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Inflammation><International><Intramural Research><Investigators><Joints><Kinetics><Laboratories><Laryngoscopy><Lesion><Life><Light><Lung Function Tests><MR Imaging><MR Tomography><MRI><Magnetic Resonance Imaging><Marrow Transplantation><Martorell Syndrome><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Medical Inspection><Methods><Monitor><Morbidity><Morbidity - disease rate><NIAMS><NIH><NMR Imaging><NMR Tomography><Nasal><Nasal Passages Nose><National Institute of Arthritis and Musculoskeletal and Skin Diseases><National Institutes of Health><Natural History><Neck><North America><Nose><Nuclear Magnetic Resonance Imaging><Occlusive Thromboaortopathy><Organ><Oscillometry><Outcome><Outcome Measure><PET><PET Scan><PET imaging><PETSCAN><PETT><Paper><Pathogenesis><Patient Recruitments><Patients><Pattern><Performance><Photoradiation><Physical Examination><Physicians><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Prediction of Response to Therapy><Progenitor Cells><Protocol><Protocols documentation><Publishing><Pulmonary function tests><Pulseless Disease><Rad.-PET><Radiography><Radiology><Radiology Specialty><Randomized Clinical Trials><Recording of previous events><Relapse><Relapsing polychondritis><Reporting><Research><Research Design><Research Personnel><Researchers><Respiratory Function Tests><Respiratory System, Nose, Nasal Passages><Reverse Coarction><Roentgenography><Role><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Sampling><Severe acute respiratory syndrome coronavirus 2><Shapes><Skin><Somatic Mutation><Source><Standardization><Steroid Compound><Steroids><Structure><Study Type><Survey Instrument><Surveys><System><Systematics><Systemic disease><Takayasu Syndrome><Takayasu's Arteritis><Temporal Arteritis><Time><Tissues><Tracheostomy><Tracheostomy procedure><Translational Research><Translational Research Enterprise><Translational Science><Treatment Efficacy><United States National Institutes of Health><Vasculitis><Waiting Lists><Work><Wuhan coronavirus><X-Ray Imaging><X-Ray Medical Imaging><Xray imaging><Xray medical imaging><Young Female Arteritis><Zeugmatography><adulthood><aged><allele variant><allelic variant><angiographic imaging><aortic inflammation><auditory tests><autoimmune disorder><base><behavior outcome><behavioral outcome><bio-markers><biobank><biologic marker><biomarker><biomarker development><biomarker discovery><biorepository><blood cell formation><cartilaginous><causation><chest CT><chest computed tomography><chronic disorder><clinical care><clinical center><clinical heterogeneity><clinical outcome prediction><clinical remission><clinical test><cohort><conventional Xray><corona virus disease 2019><coronavirus disease 2019><data standardization><data standards><deep sequencing><design><designing><developmental><diagnostic Xray><diagnostic Xray radiology><disability><disease causation><disease natural history><ethical><fluorodeoxyglucose PET><fluorodeoxyglucose positron emission tomography><genetic variant><genomic variant><hearing assessment><host response><imaging><imaging approach><imaging based approach><imaging biomarker><imaging marker><imaging study><imaging-based biological marker><imaging-based biomarker><imaging-based marker><immunoresponse><indexing><inflammation marker><inflammation of the aorta><inflammatory marker><intervention efficacy><molecular imaging><molecule imaging><mortality><new marker><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapy approaches><novel><novel biomarker><novel marker><novel therapeutic approach><novel therapeutic intervention><novel therapy approach><oscillography><pandemic><pandemic disease><participant recruitment><patient advocacy group><patient centered><patient oriented><patient subgroups><patient subpopulations><patient subsets><patient subtypes><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><predict clinical outcome><predict therapeutic response><predict therapy response><predict treatment response><predictor of clinical outcome><programs><prospective><recruit><research clinical testing><social role><standard of care><stem cells><study design><systemic autoimmunity><therapeutic efficacy><therapeutic evaluation><therapeutic testing><therapeutically effective><therapy efficacy><therapy prediction><translation research><translation research enterprise><translational medicine><translational research program><treatment prediction><treatment response prediction><trial design><uptake><vascular><vascular inflammation><vasculitides><waitlist>