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AAV pathogenesis

The development of AAV is a complex and multifactorial autoimmune process2,3

The initial causes of AAV are currently unclear.3 Predisposing factors such as microbial infection, genetic influence, environmental agents and specific drugs are all fundamental to the development of AAV.2,3

Exposure to silica, pesticides, fumes, construction materials, hydrocarbon (cleaning agents, paint, diesel), drugs (propylthiouracil, hydralazine, D-penicillamine, cefotaxime, minocycline, anti-TNF agents, phenytoin) and certain psychoactive agents may all cause AAV.2,3

References & footnotes

ANCA involvement

Loss of immune tolerance to ANCA antigens and development of ANCA by plasma cells1

ANCA are most commonly directed against the neutrophil lysosomal enzymes PR3 and MPO in GPA and MPA, respectively1-5

Neutrophils are primed

Neutrophils are primed by inflammatory cytokines (TNF-α, IL-1 and IL-18) produced in response to an infection or another event, with genetic predisposition also relevant2,6,7

ANCA antigens presented

Primed neutrophils present ANCA antigens (e.g. MPO and PR3) at their cell surface that bind to ANCA, resulting in neutrophil activation1,2,6,7

Inflammation mediators released

Activated neutrophils adhere to and penetrate the blood vessel wall, and release mediators of inflammation and cell injury, e.g. NETS1,2,6

Alternative complement pathway activated

Activated neutrophils also release factors such as properdin that have an autocrine role in activating the alternative complement pathway, leading to the generation of C5a1,6

Binding of C5a to C5aR1

Binding of C5a to C5aR1 amplifies ANCA-induced inflammation and vascular damage6

Necrotising vasculitis

This process leads to necrotising vasculitis in small blood vessels6

Chronic inflammation

Over a few days, acute inflammation and necrosis are replaced by chronic inflammation and scarring6

The importance of complement and neutrophils in AAV activation

C5a plays a major role in the pathogenesis of AAV, amplifying ANCA-induced inflammation and vascular damage1

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Introduction to AAV

Introduction to AAV

AAV is a rare, severe small vessel vasculitis that affects multiple organs and has a high acute mortality risk1

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Disease Mechanism

Disease mechanism

The interaction between the activated alternative complement pathway, neutrophilsand C5a is at the heart of vasculitic damage in AAV2

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AAV treatment

AAV treatment

A framework of practice for the treatment and management of AAV patients

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References & footnotes
EUVAS

European Vasculitis Society website

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ASN

American Society of Nephrology

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ACR

American College of Rheumatology

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ERA

European Renal Association

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EULAR

European Alliance of Associations for Rheumatology

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KDIGO

Kidney Disease Improving Global Outcomes

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KDIGO recommendations

KDIGO recommendations for the management of individuals with glomerular diseases

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Patient videos and quality of life
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Vasculitis International

Europe

www.vasculitisint.com
Selbsthilfe Vaskulitis e.V.

Germany

www.vasculitisint.com/vpag/vaskulitis-e-v/
Associazione Pazienti della Sindrome di Churg Strauss

Italy

www.apacs-egpa.org
Suomen Vaskuliittiyhdistys ry

Finland

www.vaskuliittiyhdistys.fi
Selbsthilfe Vaskulitis Mainz

Germany

vaskulitis-mainz@gmx.de
Vasculitis Stichting

Netherlands

www.vasculitis.nl
Liga Portuguesa Contra as Doencas Reumaticas

Portugal

www.lpcdr.org.pt
Association Vascularites

France/Belgium

www.association-vascularites.org

Ireland

Asociación Española de Vasculitis Sistémicas

Spain

www.sid-inico.usal.es

United Kingdom

Associazione Malattie Autoimmuni

Italy

www.associazionemalattieautoimmuni.it
Associazione Nazionale Malati Reumatici ONLUS

Italy

www.anmar-italia.it
Australia and New Zealand Vasculitis Society

Australia / New Zealand

www.anzvasculitis.org
Federación Española de Enfermedades Raras

Spain

www.enfermedades-raras.org
Liga Reumatológica Española

Spain

lire.es/
Vasculitis Stowarzyszenie Chorych

Poland

vasculitis.org.pl/