anti-neutrophil cytoplasmic autoantibodies

Last reviewed 09/2022

Antineutrophil cytoplasmic antibody (ANCA) has been shown to be a serological marker for a spectrum of diseases characterised by systemic necrotizing vasculitis and crescentic vasculitis.

The presence of ANCA characterises a group of vasculitides, including Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), and Churg–Strauss syndrome (CSS)

• ANCA testing has become routine in the diagnostic serology laboratory
  • however, because ANCA are found in a number of other settings including a range of other rheumatological diseases, inflammatory bowel disease, autoimmune liver diseases and infectious diseases as well as drug-induced syndromes, interpretation of serology results can be difficult, especially with indiscriminant ordering of ANCA testing.
  • ANCA patterns and antibody specificity ANCA describes a number of circulating autoantibodies specifically directed against the cytoplasmic constituents of neutrophils and monocytes
    • two ANCA patterns were originally identified by indirect immunofluorescence (IIF): the cytoplasmic (C-ANCA) and the perinuclear (P-ANCA) patterns
      • these apparent morphological differences are purely artefactual and based on the fixative used to preserve the neutrophil substrate
        • 'classical' C-ANCA is associated with antibodies reacting with the 29–30 kDa elastinolitic enzyme, serine proteinase 3 (PR3)
          • composed of 229 amino acids and found in the azurophilic granules of neutrophils and monocytes
        • 'classical' P-ANCA pattern is associated with antibodies to myeloperoxidase (MPO), a 140 kDa heterodymeric enzyme also associated with the antimicrobial properties of neutrophils
      • studies have shown that when the IIF and ELISA results are combined, the presence of C-ANCA and anti-PR3 has 99% specificity for the diagnosis of primary systemic vasculitis, as does the combination of P-ANCA and anti-MPO (1)
        • classical C-ANCA pattern on IIF and/or anti-PR3 are predominantly found in patients with WG
        • P-ANCA and anti-MPO are more often seen in MPA, CSS and idiopathic necrotising glomerulonephritis
      • however, additional IIF staining patterns have been described
        • termed 'atypical' ANCA and may be cytoplasmic or perinuclear
        • atypical ANCA is generally anti-PR3- and anti-MPO-negative by enzyme-linked immunosorbent assays (ELISA)
        • many of these atypical patterns have now been attributed to other antigenic molecules in the neutrophil granules such as elastase, cathepsin G, cathelicidins, lactoferin, lysosyme, bactericidal/permeability increasing protein (BPI), calprotectin and defensins
  • indications for ANCA testing:
    • patients suspected of Wegener's granulomatosis, microscopic polyangiitis, Churg–Strauss syndrome or idiopathic necrotising glomerulonephritis
    • chronic destructive disease of the upper airways Pulmonary nodules (not obviously malignant)
    • subglottic stenosis of the trachea
    • pulmonary–renal syndrome
    • glomerulonephritis
    • vasculitis of the skin with evidence of systemic disease
    • mononeuritis multiplex
    • retro-orbital mass
    • any other condition resembling systemic vasculitis

Notes:

• there is a challenge in distinguishing ANCA from other autoantibody specificities, which frequently accompany ANCA in patients with vasculitis. For example, antimicrosomal, antiribosomal and smooth muscle antibodies can easily be confused with C-ANCA, whereas antinuclear antibodies such as anti-double stranded deoxyribonucleic acid (DNA) and anti-golgi body antibodies often resemble P-ANCA

ANCA has been reported as a method for monitoring disease activity.However, while ANCA levels are useful to monitor disease and serve to alert clinicians to the possibility of relapse, they should not be the sole measure to guide therapy (1).

Reference:

1. ARC. Topical Reviews - Rheumatic Diseases: Serological Aids to Early Diagnosis. February 2006.
2. Walport MJ et al . Connective tissue diseases: advances in diagnosis and management.BJHM 1993; 50: 121-31.
3. Gaskin et al . Antimyeloperoxidases antibodies in vasculitis:relationship to ANCA and clinical diagnosis. Acta Pathol Microbiol Immuno Scand 1990;98:33.