Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides
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 po...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00680/full |
| _version_ | 1828968834207318016 |
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| author | Peter Lamprecht Anja Kerstein Sebastian Klapa Susanne Schinke Christian M. Karsten Xinhua Yu Xinhua Yu Marc Ehlers Jörg T. Epplen Jörg T. Epplen Konstanze Holl-Ulrich Thorsten Wiech Kathrin Kalies Tanja Lange Martin Laudien Tamas Laskay Timo Gemoll Udo Schumacher Sebastian Ullrich Sebastian Ullrich Hauke Busch Saleh Ibrahim Nicole Fischer Katrin Hasselbacher Ralph Pries Frank Petersen Gesche Weppner Rudolf Manz Jens Y. Humrich Relana Nieberding Gabriela Riemekasten Antje Müller |
| author_facet | Peter Lamprecht Anja Kerstein Sebastian Klapa Susanne Schinke Christian M. Karsten Xinhua Yu Xinhua Yu Marc Ehlers Jörg T. Epplen Jörg T. Epplen Konstanze Holl-Ulrich Thorsten Wiech Kathrin Kalies Tanja Lange Martin Laudien Tamas Laskay Timo Gemoll Udo Schumacher Sebastian Ullrich Sebastian Ullrich Hauke Busch Saleh Ibrahim Nicole Fischer Katrin Hasselbacher Ralph Pries Frank Petersen Gesche Weppner Rudolf Manz Jens Y. Humrich Relana Nieberding Gabriela Riemekasten Antje Müller |
| author_sort | Peter Lamprecht |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T12:19:32Z |
| format | Article |
| id | doaj.art-3c4143f1c46040ea99bc33548a389fea |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T12:19:32Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3c4143f1c46040ea99bc33548a389fea2022-12-21T23:01:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-04-01910.3389/fimmu.2018.00680336016Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated VasculitidesPeter Lamprecht0Anja Kerstein1Sebastian Klapa2Susanne Schinke3Christian M. Karsten4Xinhua Yu5Xinhua Yu6Marc Ehlers7Jörg T. Epplen8Jörg T. Epplen9Konstanze Holl-Ulrich10Thorsten Wiech11Kathrin Kalies12Tanja Lange13Martin Laudien14Tamas Laskay15Timo Gemoll16Udo Schumacher17Sebastian Ullrich18Sebastian Ullrich19Hauke Busch20Saleh Ibrahim21Nicole Fischer22Katrin Hasselbacher23Ralph Pries24Frank Petersen25Gesche Weppner26Rudolf Manz27Jens Y. Humrich28Relana Nieberding29Gabriela Riemekasten30Antje Müller31Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, GermanyDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, GermanyDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, GermanyDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, GermanyInstitute for Systemic Inflammation Research, University of Lübeck, Lübeck, GermanyXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaPriority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, GermanyLaboratories of Immunology and Antibody Glycan Analysis, Institute for Nutrition Medicine, University of Lübeck and University Medical Center Schleswig Holstein, Lübeck, GermanyDepartment of Human Genetics, Ruhr-University, Bochum, GermanyUniversity of Witten/Herdecke, ZBAF, Witten, GermanyInstitute of Pathology, Cath. Mary’s Hospital, Hamburg, GermanyInstitute of Pathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany0Institute of Anatomy, University of Lübeck, Lübeck, GermanyDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany1Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, Kiel, Germany2Department for Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany3Department of Surgery, Section for Translational Surgical Oncology and Biobanking, University of Lübeck, University Medical Center Schleswig-Holstein, Lübeck, Germany4Institute of Anatomy and Experimental Morphology, Center for Experimental Medicine, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany4Institute of Anatomy and Experimental Morphology, Center for Experimental Medicine, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany5Medical Department 3, Gastroenterology/Rheumatology, Municipal Hospital Kiel, Kiel, Germany6Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany6Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany7Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany8Department of Otorhinolaryngology, University of Lübeck, Lübeck, Germany8Department of Otorhinolaryngology, University of Lübeck, Lübeck, GermanyPriority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, GermanyDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, GermanyInstitute for Systemic Inflammation Research, University of Lübeck, Lübeck, GermanyDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, GermanyDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, GermanyDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, GermanyDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, GermanyAnti-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.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00680/fullanti-neutrophil cytoplasmic autoantibodiesanti-neutrophil cytoplasmic autoantibody vasculitidesmicroscopic polyangiitisgranulomatosis with polyangiitiseosinophilic granulomatosis with polyangiitis |
| spellingShingle | Peter Lamprecht Anja Kerstein Sebastian Klapa Susanne Schinke Christian M. Karsten Xinhua Yu Xinhua Yu Marc Ehlers Jörg T. Epplen Jörg T. Epplen Konstanze Holl-Ulrich Thorsten Wiech Kathrin Kalies Tanja Lange Martin Laudien Tamas Laskay Timo Gemoll Udo Schumacher Sebastian Ullrich Sebastian Ullrich Hauke Busch Saleh Ibrahim Nicole Fischer Katrin Hasselbacher Ralph Pries Frank Petersen Gesche Weppner Rudolf Manz Jens Y. Humrich Relana Nieberding Gabriela Riemekasten Antje Müller Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides Frontiers in Immunology anti-neutrophil cytoplasmic autoantibodies anti-neutrophil cytoplasmic autoantibody vasculitides microscopic polyangiitis granulomatosis with polyangiitis eosinophilic granulomatosis with polyangiitis |
| title | Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides |
| title_full | Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides |
| title_fullStr | Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides |
| title_full_unstemmed | Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides |
| title_short | Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides |
| title_sort | pathogenetic and clinical aspects of anti neutrophil cytoplasmic autoantibody associated vasculitides |
| topic | anti-neutrophil cytoplasmic autoantibodies anti-neutrophil cytoplasmic autoantibody vasculitides microscopic polyangiitis granulomatosis with polyangiitis eosinophilic granulomatosis with polyangiitis |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00680/full |
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