Defining Immune Tolerance in ANCA-associated Vasculitis (AAV)

Inclusion Criteria: Tolerant AAV participants: * Age 18 years or older * Diagnosis of granulomatosis with polyangiitis (Wegener's, GPA) or microscopic polyangiitis (MPA) according to the definitions of the Chapel Hill Consensus Conference (CHCC) * History of being myeloperoxidase (MPO)-ANCA positive during a disease flare * In clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) = 0 and off all immunosuppression for ≥ 2 years * Negative MPO-ANCA and proteinase 3 (PR3)-ANCA by ELISA at screening * For women of child-bearing potential, a negative urine or serum pregnancy test at the time of screening * Ability to sign and understand informed consent * Willingness to comply with study procedures. Non-Tolerant AAV participants: * Age 18 years or older * Diagnosis of granulomatosis with polyangiitis (Wegener's), GPA or microscopic polyangiitis (MPA) according to the definitions of the CHCC * History of being MPO-ANCA positive during a disease flare * Within the past 5 years, must have had a disease exacerbation, defined as an increase in the BVAS/WG score and re-institution of immunosuppressive therapy after therapy had been reduced or completely discontinued * In clinical remission with BVAS/WG = 0 and on minimal maintenance therapy for ≥3 months prior to the screening visit. Minimal maintenance therapy is defined as: * Low-dose glucocorticoids (≤10 mg of prednisone or prednisolone daily) and/or: * Azathioprine ≤ 150mg daily or * Mycophenolate mofetil (MMF) ≤ 1 gram daily or mycophenolate sodium ≤ 720 mg daily. * Positive MPO-ANCA by ELISA on at least 2 occasions within the last 52 weeks, the most recent result being within 8 weeks of visit -1 * For women of child-bearing potential, a negative urine or serum pregnancy test at the time of screening * Ability to sign and understand informed consent * Willingness to comply with study procedures. Healthy Controls: * Healthy participant age ≥18 years * For women of child-bearing potential, a negative urine or serum pregnancy test at the time of screening * Ability to sign and understand informed consent * Willingness to comply with study procedures. Exclusion Criteria: Tolerant AAV Participants: * Use of systemic intravenous (IV) or oral glucocorticoids for ˃ 1 month for any non-vasculitis indication within 8 weeks of the screening visit * Any prior treatment with rituximab * Presence of known chronic viral infections or autoimmune diseases * History of malignancy, excluding non-melanomatous skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit. Non-Tolerant AAV participants: * Use of IV pulse glucocorticoids (methylprednisolone or other) or cyclophosphamide within the year prior to the screening visit * Use of IV or oral glucocorticoids for \> 1 month for any non- vasculitis indication within 8 weeks of screening visit * Any prior treatment with rituximab * Maintenance therapy with methotrexate within 3 months of the screening visit * Presence of known chronic viral infections or other autoimmune diseases * History of malignancy, excluding non-melanoma skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit. Healthy Controls: * Use of IV or oral glucocorticoids for \> 1 month for any non-vasculitis indication within 8 weeks of the screening visit * Presence of known chronic viral infections or other autoimmune diseases * History of malignancy, excluding non-melanoma skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit. AAV Participants Discontinuing Immunosuppression: * Any prior treatment with rituximab * Maintenance therapy with methotrexate within 3 months of the screening visit * Presence of known chronic viral infections or other autoimmune diseases * History of malignancy, excluding non-melanoma skin cancers or cervical cancer carcinoma in situ, within 5 years of the screening visit.