ANCA-associated vasculitis

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.

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Fig. 1: Small vessel vasculitis.
Fig. 2: Global epidemiology of ANCA-associated vasculitides.
Fig. 3: Pathogenetic events in GPA and MPA.
Fig. 4: Loss of tolerance and the generation of effector responses in GPA and MPA.
Fig. 5: Endothelial and tissue injury in GPA and MPA.
Fig. 6: Clinical features of AAV.
Fig. 7: Histopathology of AAV.
Fig. 8: Management of GPA and MPA cases that present with organ or life-threatening manifestations.

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Acknowledgements

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).

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All authors contributed to all sections of the Primer, with A.R.K. coordinating the project. The middle authors of the Primer are listed in alphabetical order.

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Correspondence to A. Richard Kitching.

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A.R.K. is Chair of the Board of the Australian and New Zealand Vasculitis Society and has been a consultant for CSL Limited and Visterra. N.B. has received research funding from Vifor and GSK and speaking fees from Roche and Vifor. E.B. received consultancy and speaker fees from Roche, which were paid to her employer. D.R.J. has been a consultant for ChemoCentryx, InflaRx and Insmed. P.A.L. holds founding equity in and receives consultation fees from PredictImmune Ltd. P.A.M. has been a consultant for AbbVie, Biogen, CSL Behring, Genzyme, Insmed, Janssen, Kiniska and Sparrow, received research funding and consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, Genentech/Roche, GSK and InflaRx, and grant support from Kypha. U.S. has been a consultant for AstraZeneca, Insmed, and ChemoCentryx and has received research funding from Genentech, Bristol-Myers Squibb, ChemoCentryx and GSK. The remaining authors declare no competing interests.

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Nature Reviews Disease Primers thanks P. Van Paassen, B. Hellmich, M.-H. Zhao, A. Vaglio, M. Segelmark and X. Puéchal for their contribution to the peer review of this work.

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Kitching, A.R., Anders, HJ., Basu, N. et al. ANCA-associated vasculitis. Nat Rev Dis Primers 6, 71 (2020). https://doi.org/10.1038/s41572-020-0204-y

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