Antineutrophil cytoplasmic antibodies (ANCA) and systemic vasculitis: Update of assays, immunopathogenesis, controversies, and report of a novel de novo ANCA-associated vasculitis after kidney transplantation

Objectives: To characterize antineutrophil cytoplasmic antibodies (ANCA), t heir major autoantigens, disease associations, and pathophysiology in syste mic vasculitides. To describe a patient with a novel de novo ANCA-associate d vasculitis after kidney transplantation. Methods: We reviewed and compiled the literature on ANCA-related topics and systemic vasculitis, Laboratory and clinical data from a cadaveric kidney transplant patient who developed necrotizing vasculitis involving glomerula r capillaries, with crescent formation associated with P-ANCA and myelopero xidase, were analyzed. Results: Large-scale multi-center testing of patient and normal sera by the European ANCA Assay Standardization Project using immunofluorescence assay s and enzyme immunoassays indicate the assays have good sensitivity and spe cificity, and diagnostic utility for ANCA-associated vasculitis, A few inve stigations covering basic and clinical research with ANCA remain controvers ial: whether endothelial cells do or do not express a 29-kd neutral serine protease termed proteinase-3 (PR-3), the target of ANCA in most individuals with Wegener's granulomatosis, and whether anti-myeloperoxidase (MPO) ANCA s recognize a restricted number of epitopes on MPO. This issue has relevanc e for using monoclonal antibodies to treat patients with vasculitis who hav e adverse effects from immunosuppressive drugs. The two allelic forms of Fc gamma RIIa (H131/R131) and the two of Fc gamma RIIIb (NA1/NA2) are discuss ed as possible inheritable genetic elements for vasculitic disorders and fo r signaling responses. Stimulatory and costimulatory molecules, and cytokin e profiles of T lymphocytes are characterized to show that these cells are actively involved in the ANCA-associated vasculitides. The patient describe d had a de novo ANCA associated small vessel vasculitis which developed aft er renal transplantation. Conclusions: There have been significant advances in the development of sen sitive and specific ANCA assays. The immunopathogenetic mechanism of ANCA i nvolves the constitutive Fc gamma Rs, ligands, and signaling responses to a ctivate cytokine-primed neutrophils. This may lead to the generation of rea ctive oxygen intermediates, degranulation, and secretion of intracellular g ranule contents, and ultimately inflammation and vasculitis. Copyright (C) 2000 by W.B. Saunders Company.