ANCA-associated vasculitis

Kitching, A. R., Anders, H.-J. and Basu, N. (2020) ANCA-associated vasculitis. Nature Reviews Disease Primers, 6, 71. (doi: 10.1038/s41572-020-0204-y) (PMID:32855422)

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.

• Item Type: Articles
• Additional Information: H-J.A., E.B., R.K., P.A.L. and A.R.K. are principle investigators, and J.K and C.O.S.S. are scientific advisers of the European Union Horizon 20/20 RELENT (RELapses prevENTion in chronic autoimmune disease) consortium that has received funding from the European Union Horizon 2020 research and innovation programme under grant agreement 668036. A.R.K. acknowledges funding support from the Australian National Health and Medical Research Council of Australia (grant numbers 1104422, 1084869 and 1115805). H-J.A. was supported by the Deutsche Forschungsgemeinschaft (grant number AN372/24-1). P.A.L. acknowledges support from the Medical Research Council (grant number MR/L019027/1), Versus Arthritis (grant number 20593) and the British Heart Foundation (grant number PG/13/64/30435).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Basu, Professor Neil
• Authors: Kitching, A. R., Anders, H.-J., and Basu, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Nature Reviews Disease Primers
• Publisher: Nature Research
• ISSN: 2056-676X
• ISSN (Online): 2056-676X
• Copyright Holders: Copyright © 2020 Springer Nature
• First Published: First published in Nature Reviews Disease Primers 6:71
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher