TY - JOUR
T1 - Antineutrophil cytoplasmic antibodies (ANCA) and systemic vasculitis
T2 - Update of assays, immmunopathogenesis, controversies, and report of a novel de novo ANCA-associated vasculitis after kidney transplantation
AU - Schultz, Duane R.
AU - Diego, Jorge M.
PY - 2000/1/1
Y1 - 2000/1/1
N2 - Objectives: To characterize antineutrophil cytoplasmic antibodies (ANCA), their major autoantigens, disease associations, and pathophysiology in systemic vasculitides. To describe a patient with a novel de novo ANCA- associated 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 glomerular capillaries, with crescent formation associated with P-ANCA and myeloperoxidase, were analyzed. Results: Large-scale multi-center testing of patient and normal sera by the European ANCA Assay Standardization Project using immunofluorescence assays and enzyme immunoassays indicate the assays have good sensitivity and specificity, and diagnostic utility for ANCA-associated vasculitis. A few investigations coveting basic and clinical research with ANCA remain controversial: 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) ANCAs recognize s restricted number of epitopes on MPO. This issue has relevance for using monoclonal antibodies to treat patients with vasculitis who have adverse effects from immunosuppressive drugs. The two allelic forms of FcγRIIa (H131/R131) and the two of FcγRIIIb (NA1/NA2) are discussed as possible inheritable genetic elements for vasculitic disorders and for signaling responses. Stimulatory and costimulatory molecules, and cytokine profiles of T lymphocytes are characterized to show that these cells are actively involved in the ANCA-associated vasculitides. The patient described had a de novo ANCA associated small vessel vasculitis which developed after renal transplantation. Conclusions: There have been significant advances in the development of sensitive and specific ANCA assays. The immunopathogenetic mechanism of ANCA involves the constitutive FcγRs, ligands, and signaling responses to activate cytokine-primed neutrophils. This may lead to the generation of reactive oxygen intermediates, degranulation and secretion of intracellular granule contents, and ultimately inflammation and vasculitis. Copyright (C) 2000 W.B. Saunders Company.
AB - Objectives: To characterize antineutrophil cytoplasmic antibodies (ANCA), their major autoantigens, disease associations, and pathophysiology in systemic vasculitides. To describe a patient with a novel de novo ANCA- associated 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 glomerular capillaries, with crescent formation associated with P-ANCA and myeloperoxidase, were analyzed. Results: Large-scale multi-center testing of patient and normal sera by the European ANCA Assay Standardization Project using immunofluorescence assays and enzyme immunoassays indicate the assays have good sensitivity and specificity, and diagnostic utility for ANCA-associated vasculitis. A few investigations coveting basic and clinical research with ANCA remain controversial: 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) ANCAs recognize s restricted number of epitopes on MPO. This issue has relevance for using monoclonal antibodies to treat patients with vasculitis who have adverse effects from immunosuppressive drugs. The two allelic forms of FcγRIIa (H131/R131) and the two of FcγRIIIb (NA1/NA2) are discussed as possible inheritable genetic elements for vasculitic disorders and for signaling responses. Stimulatory and costimulatory molecules, and cytokine profiles of T lymphocytes are characterized to show that these cells are actively involved in the ANCA-associated vasculitides. The patient described had a de novo ANCA associated small vessel vasculitis which developed after renal transplantation. Conclusions: There have been significant advances in the development of sensitive and specific ANCA assays. The immunopathogenetic mechanism of ANCA involves the constitutive FcγRs, ligands, and signaling responses to activate cytokine-primed neutrophils. This may lead to the generation of reactive oxygen intermediates, degranulation and secretion of intracellular granule contents, and ultimately inflammation and vasculitis. Copyright (C) 2000 W.B. Saunders Company.
KW - Antineurophil cytoplasmic antibodies
KW - Fcγ receptors
KW - Myeloperoxidase
KW - Proteinase- 3
KW - Vasculitic diseases
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U2 - 10.1016/S0049-0172(00)80014-1
DO - 10.1016/S0049-0172(00)80014-1
M3 - Article
C2 - 10805352
AN - SCOPUS:0034105883
VL - 29
SP - 267
EP - 285
JO - Seminars in Arthritis and Rheumatism
JF - Seminars in Arthritis and Rheumatism
SN - 0049-0172
IS - 5
ER -