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ANCA-assoziierte Vaskulitiden: Neuere Aspekte der Entstehung [Antineutrophil cytoplasmic antibody-associated vasculitis: novel aspects in the pathogenesis]

Item Type:Article
Title:ANCA-assoziierte Vaskulitiden: Neuere Aspekte der Entstehung [Antineutrophil cytoplasmic antibody-associated vasculitis: novel aspects in the pathogenesis]
Creators Name:Schreiber, A., Choi, M. and Kettritz, R.
Abstract:Antineutrophil cytoplasmic antibodies (ANCA) occur in patients with small vessel vasculitis and necrotizing crescentic glomerulonephritis. The main target antigens are proteinase 3 (PR3) and myeloperoxidase (MPO). Novel findings implicate lysosomal-associated membrane protein 2 (LAMP-2) as an additional antigen and epigenetic mechanisms as important transcriptional regulators for PR3 and MPO expression. Generation of ANCAs is a consequence of a complex interplay between antigen presentation, T-cells and B-cells. Recent data underline the significance of distinct CD4+T-cell subsets. A complementary PR3 protein has been identified which not only triggers the generation of anti-idiotypic antibodies recognizing PR3 but also constituents of the coagulation cascade. Additional important ANCA-induced neutrophil and monocyte effector functions were identified, such as the formation of DNA-containing neutrophil extracellular traps (NETs), the activation of a specific phosphatidylinositol-3 kinase isoform and the neutrophil serine protease-dependent IL-1{beta} generation. Animal models allow testing of treatment strategies which target these new molecules.
Keywords:Vasculitis, Antineutrophil Cytoplasmic Antibodies, Pathogenesis, Leukocytes, Animal Models, Animals, Mice
Source:Nephrologe
ISSN:1862-040X
Publisher:Springer
Volume:7
Number:3
Page Range:192-199
Date:May 2012
Official Publication:https://doi.org/10.1007/s11560-011-0606-7

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