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Principal Investigator: Peter Grayson
Organization: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
Fiscal Year: 2024
Award: $2,975,025
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 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 1000 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 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 few years, 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.
Terms: <21+ years old><ANCA associated vasculitis><ANCA vasculitis><Adult><Adult Human><Angiitis><Anti-neutrophil cytoplasmic antibody associated vasculitis><Anti-neutrophil cytoplasmic antibody related vasculitis><Anti-neutrophil cytoplasmic antibody vasculitis><Anti-neutrophil cytoplasmic antigen induced vasculitis><Anti-neutrophil cytoplasmic autoantibody associated vasculitis><Anti-neutrophil cytoplasmic autoantibody vasculitis><Aortitis><Area><Arteries><Audiogram><Audiometric Test><Audiometry><Autoimmune Diseases><Biological Markers><Biological Specimen Banks><Biological Substance Banks><Blood Vessels><Body Tissues><Bone Marrow><Bone Marrow Grafting><Bone Marrow Reticuloendothelial System><Bone Marrow Transplant><Bone Marrow Transplantation><Brachiocephalic Ischemia><COVID-19 affected><COVID-19 consequence><COVID-19 effect><COVID-19 exposure><COVID-19 impact><COVID-19 impacted><Causality><Chronic Disease><Chronic Illness><Classification><Clinical><Clinical Evaluation><Clinical Research><Clinical Study><Clinical Testing><Clinical Trials><Clinical Trials Database><Clinical assessments><Collaborations><Communication><Complex><Cranial Arteritis><Data><Data Collection><Dedications><Development><Diagnosis><Diagnostic tests><Disease><Disease Management><Disease Progression><Disorder><Disorder Management><EXTMR><Ear><Enzyme Gene><Enzymes><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Ethics><Etiology><Evaluation><Extramural><Extramural Activities><FDG PET><Foundations><Future><Gene variant><General Prognostic Factor><General Radiology><Genetic><Germ-Line Mutation><Germline Mutation><Giant Cell Arteritis><Goals><Health behavior><Hearing Tests><Hematology><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><Intramural Research><Investigators><Joints><Laboratories><Laryngoscopy><Lead><Lesion><Life><Light><Link><Lung Function Tests><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Marrow Transplantation><Martorell Syndrome><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Medical Inspection><Methods><Molecular><Monitor><Morbidity><Morbidity - disease rate><Musculoskeletal Pain Disorder><NGS Method><NGS system><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><PET><PET Scan><PET imaging><PETSCAN><PETT><Pathogenesis><Patient Selection><Patients><Pattern><Pb element><Photoradiation><Physical Examination><Physicians><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Prediction of Response to Therapy><Prognostic Factor><Prognostic/Survival Factor><Protocol><Protocols documentation><Publishing><Pulmonary function tests><Pulseless Disease><Rad.-PET><Radiography><Radiology><Radiology Specialty><Recording of previous events><Relapse><Relapsing polychondritis><Reporting><Research><Research Design><Research Personnel><Researchers><Respiratory System, Nose, Nasal Passages><Reverse Coarction><Rheumatic Diseases><Rheumatism><Rheumatologic Diseases><Rheumatologic Disorder><Roentgenography><Role><SARS-CoV-2 exposure><SARS-CoV2 exposure><Sampling><Severe acute respiratory syndrome coronavirus 2 exposure><Shapes><Somatic Mutation><Source><Steroid Compound><Steroids><Structure><Study Type><Survey Instrument><Surveys><Syndrome><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><Vacuole><Vasculitis><Work><Young Female Arteritis><Zeugmatography><adulthood><aged><allele variant><allelic variant><aortic inflammation><auditory tests><autoimmune condition><autoimmune disorder><autoimmunity disease><autoinflammatory><bio-markers><biobank><biologic marker><biological specimen repository><biomarker><biomarker development><biomarker discovery><biorepository><biosample repository><biospecimen bank><biospecimen repository><cartilaginous><causation><chest CT><chest computed tomography><chronic disorder><clinical care><clinical center><clinical heterogeneity><clinical outcome measures><clinical remission><clinical test><cohort><coronavirus disease 2019 consequence><coronavirus disease 2019 effect><coronavirus disease 2019 exposure><coronavirus disease 2019 impact><coronavirus disease-19 impact><data standardization><data standards><design><designing><developmental><diagnostic algorithm><disability><disease causation><disease heterogeneity><disease natural history><epidemiologic investigation><epidemiology study><ethical><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><fluorodeoxyglucose PET><fluorodeoxyglucose positron emission tomography><genetic variant><genomic variant><germ-line defect><germline variant><health related behavior><hearing assessment><heavy metal Pb><heavy metal lead><histories><host response><imaging><imaging biomarker><imaging marker><imaging-based biological marker><imaging-based biomarker><imaging-based marker><immune system response><immunoresponse><indexing><inflammation marker><inflammation of the aorta><inflammatory marker><intervention efficacy><molecular imaging><molecule imaging><mortality><new marker><next gen sequencing><next generation sequencing><nextgen sequencing><novel><novel biomarker><novel marker><observational cohort study><oscillography><pandemic><pandemic disease><pandemic effect><pandemic impact><pandemic outcome><pandemic repercussions><patient advocacy group><patient centered><patient oriented><patient subclass><patient subcluster><patient subgroups><patient subpopulations><patient subsets><patient subtypes><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><physical examinations><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><predict clinical outcome><predict therapeutic response><predict therapy response><programs><prospective><radiologic imaging><radiological imaging><randomized, clinical trials><recruit><research clinical testing><social role><somatic variant><specimen bank><specimen repository><standard of care><study design><therapeutic efficacy><therapeutic evaluation><therapeutic testing><therapy efficacy><therapy prediction><translation research><translation research enterprise><translational investigation><translational medicine><translational research program><treatment prediction><treatment response prediction><trial design><vascular><vascular inflammation><vasculitides>