000K utf8 1100 $c2018 1500 eng 2050 urn:nbn:de:gbv:8:3-2021-00881-5 2051 10.3389/fimmu.2018.00680 3000 Lamprecht, Peter 3010 Busch, Hauke 3010 Ehlers, Marc 3010 Epplen, Jörg T 3010 Fischer, Nicole 3010 Gemoll, Timo 3010 Hasselbacher, Katrin 3010 Holl-Ulrich, Konstanze 3010 Humrich, Jens Y 3010 Ibrahim, Saleh 3010 Kalies, Kathrin 3010 Karsten, Christian M 3010 Kerstein, Anja 3010 Klapa, Sebastian 3010 Lange, Tanja 3010 Laskay, Tamas 3010 Laudien, Martin 3010 Manz, Rudolf 3010 Müller, Antje 3010 Nieberding, Relana 3010 Petersen, Frank 3010 Pries, Ralph 3010 Riemekasten, Gabriela 3010 Schinke, Susanne 3010 Schumacher, Udo 3010 Ullrich, Sebastian 3010 Weppner, Gesche 3010 Wiech, Thorsten 3010 Yu, Xinhua 4000 Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides [Lamprecht, Peter] 4209 Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV. 4950 https://doi.org/10.3389/fimmu.2018.00680$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2021-00881-5$xR$3Volltext$534 4961 https://macau.uni-kiel.de/receive/macau_mods_00002297 5051 610 5550 Animals 5550 Antibodies, Antineutrophil Cytoplasmic 5550 Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis 5550 Anti-neutrophil Cytoplasmic Autoantibodies 5550 Anti-neutrophil Cytoplasmic Autoantibody Vasculitides 5550 B-Lymphocytes 5550 Cell Death 5550 Complement Pathway, Alternative 5550 Eosinophilic Granulomatosis With Polyangiitis 5550 Granulomatosis With Polyangiitis 5550 Humans 5550 Immunoglobulin G 5550 Microscopic Polyangiitis