Project Summary/Abstract The systemic vasculitides are a group of rare diseases characterized by severe inflammation of blood vessels leading to arterial stenosis or occlusion, and organ damage or death if untreated. With aggressive immunosuppressive treatment, most patients survive, but subsequent disease course is variable, relapse is common, and long-term morbidity from vasculitis or its treatment is expected. Long-term longitudinal studies are needed to inform and guide clinicians in this era of adequate but imperfect management. There are also significant unmet needs for i) biomarkers of disease activity, risk of relapse, and long-term damage; ii) genetic epidemiology studies to provide insight into pathogenesis and ideas for therapeutics; iii) early-phase clinical trials of novel therapeutics; iv) novel methods to conduct high-quality clinical trials and clinical research studies in these rare diseases; and v) for improved outcome measures, including patient-reported outcomes. The Vasculitis Clinical Research Consortium (VCRC) Longitudinal Study address all these unmet needs through the multiple research studies associated with this protocol. We propose to continue conducing the VCRC Longitudinal Study to study nine vasculitides: giant cell arteritis, Takayasu's arteritis, polyarteritis nodosa, granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, idiopathic aortitis, central nervous system vasculitis, and relapsing polychondritis at leading referral centers internationally. The Longitudinal Study provides data and samples to the VCRC Clinical Data, Biospecimen, and Tissue Repositories. The VCRC makes all of our data and specimens available to any investigator seeking to conduct scientifically valid research that will advance our understanding of vasculitis. The Longitudinal Study has been remarkably successful and scientifically productive. More than 2000 patients have been enrolled and more that 75 projects launched related to the data and specimens generated in the Longitudinal Study. The VCRC Longitudinal Study is a remarkable and unique resource that provides the means to study a group of rare diseases in a comprehensive, prospective, standardized manner and produce data and linked biologic material unprecedented and otherwise unavailable in the field of clinical research in vasculitis. The Longitudinal Study runs smoothly within the Rare Diseases Clinical Research Network and is synergistic and vital to other operations and studies of the Consortium. The U54 grant provides vital support for the Longitudinal Study that in turn provides opportunities for clinician scientists throughout the world.