Antineutrophil cytoplasmic antibodies: Major autoantigens, pathophysiology, and disease associations

Duane R. Schultz, Elaine C. Tozman

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Antineutrophil cytoplasmic antibodies (ANCA) are important serological markersfor the primary systemic vasculitides, including microscopic polyarteritis and necrotizing crescentic glomerulonephritis. Numerous reports have established the clinical utility of ANCA titer in monitoring disease activity, relapses, and response to treatment. ANCA, detected by indirect immunofluorescence (IIF) assays using patient's serum and ethanol-fixed human neutrophils, produce two common fluorescent staining patterns: cytoplasmic (C-ANCA), involving a 29-kD neutral serine protease termed proteinase 3 (PR3), and perinuclear (P-ANCA), the result mainly of myeloperoxidase (MPO), but occasionally by other components of the azurophilic granules including lysozyme, elastase, cathepsins, and lactoferrin. Some sera contain granulocyte-specific antinuclear antibodies (GS-ANA), which require formaldehyde fixation of neutrophils to cross link cytoplasmic antigens for distinguishing between ANCA and the GS-ANA by IIF. Positive IIF is confirmed by Western blot analysis or specific enzyme-linked immunosorbent assay for PR3, MPO, and other neutrophil granule antigens. The C-ANCA pattern is highly specific for Wegener's granulomatosis, a disease characterized by granulomatous inflammation, necrotizing and crescentic glomerulonephritis, and vasculitis; P-ANCA is found in sera of individuals with vasculitis, glomerulonephritis, and several other diseases. ANCA are predominantly immunoglobulin (Ig)G isotype, but may be IgM and IgA. Various pathophysiologic mechanisms have been proposed involving ANCA-mediated neutrophil activation in a hypothetical model of vasculitic diseases: positive signals via the FcγRII (CD32) receptor after IgG-ANCA binding to membrane-associated PR3, relevant cytokines, production of adhesion molecules on both activated neutrophils and endothelial cells, and the release of neutrophil reactive oxygen species and degranulation causing endothelial cell damage. Interference of C-ANCA with PR3 proteolysis and PR3 inhibition physiologically by the α1-proteinase inhibitor may have a pathogenic role. No convincing data have been reported for the existence of autoreactive T lymphocytes reactive to any degree with the neutrophil azurophilic enzymes. Studies of various drug- and infectious agent-related diseases and ANCA may contribute to understanding the mechanism(s) involved in some vasculitides.

Original languageEnglish (US)
Pages (from-to)143-159
Number of pages17
JournalSeminars in Arthritis and Rheumatism
Issue number3
StatePublished - Dec 1995


  • A-ANCA
  • ANCA
  • antineutrophil cytoplasmic antibodies
  • Antineutrophil cytoplasmic antibody
  • atypical ANCA
  • C-ANCA
  • cathepsin G
  • CG
  • cytoplasmic ANCA
  • enzyme-linked immunosorbent assay
  • FcyRII
  • granulocyte-specific antinuclear autoantibodies
  • GS-ANA
  • Henoch-Schönlein purpura
  • HLE
  • HSP
  • human leukocyte elastase
  • Ig
  • IIF
  • immunoglobulin
  • indirect immunofluorescence
  • MPO
  • myeloperoxidase
  • P-ANCA
  • perinuclear ANCA
  • PR3
  • proteinase-3
  • r
  • recombinant
  • SDS
  • sIL-2R
  • sodium dodecylsulfate
  • soluble interleukin-2 receptor
  • the second receptor for the Fc fragment of IgG
  • TNF-α
  • tumor necrosis factor alpha
  • vasculitis
  • Wegener's granulomatosis
  • WG
  • α-PI
  • α-proteinase inhibitor

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Rheumatology
  • Orthopedics and Sports Medicine


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