ANCA-Associated Vasculitis

ANCA-associated vasculitis is a group of small-vessel vasculitides associated with anti-neutrophil cytoplasmic antibodies (ANCA) and characterised in the kidney by a pauci-immune, often crescentic, necrotising glomerulonephritis. It encompasses granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis, and is a leading cause of rapidly progressive glomerulonephritis in adults.

Definition

ANCA-associated vasculitis is a necrotising small-vessel vasculitis associated with circulating anti-neutrophil cytoplasmic antibodies, which in the kidney produces a pauci-immune (scant immune deposit) frequently crescentic glomerulonephritis and is classified into granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis.

Scope

This entry describes the disease group, the role of ANCA directed against proteinase 3 (PR3) and myeloperoxidase (MPO), the pauci-immune renal lesion, and the place of these diseases within the Chapel Hill classification of vasculitides. It is a reference description of mechanism, classification, and the evidence base; it does not provide diagnostic thresholds or treatment recommendations, which rest with current guidelines and treating clinicians.

Core questions

• How do ANCA against PR3 and MPO relate to the small-vessel injury?
• Why is the renal lesion described as pauci-immune despite active inflammation?
• How do the clinical subtypes within the ANCA-associated group differ?
• What evidence underlies the modern framework for remission induction in these diseases?

Key concepts

• Anti-neutrophil cytoplasmic antibodies (ANCA)
• PR3-ANCA and MPO-ANCA
• Pauci-immune necrotising glomerulonephritis
• Crescentic glomerulonephritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis
• Eosinophilic granulomatosis with polyangiitis
• Chapel Hill Consensus nomenclature

Mechanisms

In ANCA-associated vasculitis, antibodies directed against neutrophil granule constituents — most often proteinase 3 (PR3) or myeloperoxidase (MPO) — are thought to activate primed neutrophils, which then adhere to and damage small-vessel walls, releasing toxic granule contents and generating necrotising inflammation. In the glomerulus this produces focal necrosis and crescent formation with little immunoglobulin deposition on immunofluorescence, hence the term pauci-immune, distinguishing it from immune-complex and anti-GBM disease. The serologic ANCA type (PR3 versus MPO) correlates with clinical and prognostic patterns and is increasingly used alongside the clinicopathologic subtypes for classification (Jennette 2012; Floege 2018).

Clinical relevance

Recognition of a pauci-immune crescentic lesion with positive ANCA places a presentation within this disease group and connects it to a substantial controlled-trial evidence base. This entry summarises the mechanism, classification, and high-level evidence for reference and education; it does not specify diagnostic criteria, dosing, or individualised treatment, which are governed by current guidelines and treating clinicians.

Epidemiology

ANCA-associated vasculitis is uncommon but is among the most frequent causes of rapidly progressive glomerulonephritis, particularly in older adults. The relative frequency of PR3- versus MPO-associated disease and of the clinical subtypes varies by geography and ancestry (Jennette 2012; Rovin 2021).

History

The recognition of ANCA in the 1980s linked a serologic marker to a previously heterogeneous set of small-vessel vasculitides and reframed their pathogenesis around neutrophil activation. The Chapel Hill Consensus Conferences standardised nomenclature, and a series of randomised trials — including the RAVE trial comparing rituximab with cyclophosphamide for remission induction — established the modern evidence framework for these diseases (Jennette 2012; Stone 2010; Specks 2013).

Debates

Should classification be serologic (PR3 vs MPO) or clinicopathologic (named syndromes)?

ANCA specificity (PR3 versus MPO) correlates with genetics, relapse risk, and outcome, prompting debate over whether serologic categories better capture the biology than the traditional named syndromes; current frameworks often combine both.

Key figures

• J. Charles Jennette
• Ronald J. Falk
• John H. Stone
• Ulrich Specks

Seminal works

• jennette2012
• stone2010
• specks2013

Frequently asked questions

What does 'pauci-immune' mean in this context?

It means that, despite active necrotising inflammation in the glomerulus, immunofluorescence shows little or no immunoglobulin or complement deposition, which distinguishes ANCA-associated glomerulonephritis from immune-complex and anti-GBM disease.

What is the difference between PR3-ANCA and MPO-ANCA disease?

They are defined by the target antigen of the autoantibody — proteinase 3 or myeloperoxidase — and differ in associated clinical syndromes, genetics, and relapse tendency, which is why ANCA specificity is reported as part of classification.