Antineutrophil cytoplasmic antibody

Last revised by Daniel J Bell on 24 Nov 2020

Antineutrophil cytoplasmic antibodies (ANCAs) are a heterogenous class of IgG autoantibodies raised against the cellular contents of neutrophils, monocytes and endothelial cells 1. Under indirect immunofluorescence (IIF) microscopy, three ANCA staining patterns are observed, based on the varying intracellular distribution of their antigenic targets 2:

  • perinuclear (p-ANCA)
    • classical antigen specificity: myeloperoxidase (MPO-ANCA), an enzyme present in neutrophil azurophilic granules and monocyte lysosomes
    • a broad array of non-MPO p-ANCA antigen specificities are described (e.g. elastase, lysozyme), each with subtle variations in IIF staining (which may class them as atypical)
  • cytoplasmic (c-ANCA)
    • classical antigen specificity: proteinase-3 (PR3-ANCA), present in neutrophil azurophilic granules
    • other atypical c-ANCA antigens exist, but are poorly described and many remain largely unknown
  • atypical (a-ANCA)
    • commonly demonstrates a pattern of combined perinuclear and cytoplasmic staining

ANCAs are implicated in both the initiation and amplification of vasculitic disease, due to their ability to directly activate cytokine-primed neutrophils, leading to increased neutrophil adhesion and diapedesis 1,3. Neutrophils degranulate and become necrotic, secondary to altered apoptotic signaling as a result of ANCA binding. Inflammatory cells (e.g. neutrophils, monocytes), and more ANCA antibodies are recruited, perpetuating endothelial damage and vasculitis in a vicious cycle 1,3.

ANCAs not directed against MPO or PR3 are commonly associated with non-vasculitic inflammatory diseases 1,4. Diseases associated with high ANCA titer include 4:

History and etymology

ANCAs were first described in 1982 by Davies et al. in patients with segmental necrotizing glomerulonephritis and glomerulitis with polyangiitis 5.

ADVERTISEMENT: Supporters see fewer/no ads

Updating… Please wait.

 Unable to process the form. Check for errors and try again.

 Thank you for updating your details.