@Article{macau_mods_00002297, author = {Lamprecht, Peter and Kerstein, Anja and Klapa, Sebastian and Schinke, Susanne and Karsten, Christian M. and Yu, Xinhua and Ehlers, Marc and Epplen, J{\"o}rg T. and Holl-Ulrich, Konstanze and Wiech, Thorsten and Kalies, Kathrin and Lange, Tanja and Laudien, Martin and Laskay, Tamas and Gemoll, Timo and Schumacher, Udo and Ullrich, Sebastian and Busch, Hauke and Ibrahim, Saleh and Fischer, Nicole and Hasselbacher, Katrin and Pries, Ralph and Petersen, Frank and Weppner, Gesche and Manz, Rudolf and Humrich, Jens Y. and Nieberding, Relana and Riemekasten, Gabriela and M{\"u}ller, Antje}, title = {Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides}, journal = {Frontiers in immunology}, year = {2018}, publisher = {Frontiers Media SA}, address = {Lausanne}, volume = {9}, keywords = {B-Lymphocytes; Animals; Humans; Immunoglobulin G; Antibodies, Antineutrophil Cytoplasmic; Cell Death; Complement Pathway, Alternative; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Granulomatosis With Polyangiitis; Eosinophilic Granulomatosis With Polyangiitis; Anti-neutrophil Cytoplasmic Autoantibodies; Anti-neutrophil Cytoplasmic Autoantibody Vasculitides}, abstract = {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.}, issn = {1664-3224}, doi = {10.3389/fimmu.2018.00680}, url = {https://macau.uni-kiel.de/receive/macau_mods_00002297}, url = {https://doi.org/10.3389/fimmu.2018.00680}, url = {http://www.ncbi.nlm.nih.gov/pubmed/29686675}, file = {:https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/macau_derivate_00003394/fimmu-09-00680.pdf:PDF}, language = {en} }