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ANCA-associated vasculitis

Author

Nat Rev Dis Primers. 2020 Aug 27;6(1):71. doi: 10.1038/s41572-020-0204-y.

A Richard Kitching 1 2, Hans-Joachim Anders 3, Neil Basu 4, Elisabeth Brouwer 5, Jennifer Gordon 6, David R Jayne 7, Joyce Kullman 8, Paul A Lyons 7 9, Peter A Merkel 10, Caroline O S Savage 11, Ulrich Specks 12, Renate Kain 13

Author Information

1 Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia. richard.kitching@monash.edu.

2 Departments of Nephrology and Paediatric Nephrology, Monash Health, Clayton, Victoria, Australia. richard.kitching@monash.edu.

3 Renal Division, Medizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians University, Munich, Germany.

4 Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.

5 Vasculitis Expertise Centre Groningen, Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.

6 Department of Neuroscience and Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA, USA.

7 Department of Medicine, University of Cambridge School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.

8 Vasculitis Foundation, Kansas City, MO, USA.

9 Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.

10 Division of Rheumatology, Department of Medicine and Division of Clinical Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA.

11 Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

12 Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

13 Department of Pathology, Medical University Vienna, Vienna, Austria.

Abstract

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients.