What is the ANCA (Antineutrophil Cytoplasmic Antibody) test used for?

ANCA Test: Primary Diagnostic Tool for Systemic Vasculitis

The ANCA (Antineutrophil Cytoplasmic Antibody) test is primarily used to diagnose ANCA-associated vasculitides (AAV), specifically granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA)—life-threatening systemic vasculitides affecting small blood vessels. 1

Primary Disease Associations

C-ANCA (PR3-ANCA) Pattern

• Granulomatosis with polyangiitis (GPA): Present in 80-90% of active systemic disease, though sensitivity drops to 50% in limited forms or after corticosteroid therapy 2, 1
• Microscopic polyangiitis: Found in 20-40% of cases 1
• EGPA: Detected in 35% of cases 1
• Pauci-immune crescentic glomerulonephritis: Present in 20-40% of cases 1

P-ANCA (MPO-ANCA) Pattern

• Microscopic polyangiitis: Most commonly associated, present in 35-40% of patients 3
• EGPA: Found in 30-40% of patients, particularly those with glomerulonephritis, peripheral neuropathy, and purpura 2, 3
• Note: Approximately 5% of GPA patients can have positive P-ANCA/MPO, requiring careful differential diagnosis 3

Recommended Testing Methodology

The American College of Rheumatology now recommends high-quality antigen-specific immunoassays (ELISA) for PR3-ANCA and MPO-ANCA as the primary screening method, without categorical need for indirect immunofluorescence (IIF) first. 1, 4 This represents a shift from the older 1999 consensus that required IIF screening first 4.

• Perform both MPO-ANCA and PR3-ANCA testing simultaneously using ELISA 1
• If immunoassay is negative but clinical suspicion remains high, consider a second test (either another immunoassay or IIF) 5
• IIF may still be useful when testing for non-vasculitic conditions (autoimmune hepatitis, inflammatory bowel disease) where target antigens are not well characterized 6

When to Order ANCA Testing

Mandatory Testing Scenarios

• Any patient with clinical features suggesting ANCA-associated vasculitis 6
• All patients with anti-GBM disease 6
• Idiopathic interstitial pneumonia 6
• Infective endocarditis associated with nephritis 6
• All patients with suspected EGPA (asthma, eosinophilia, rhinosinusitis, lung infiltrates) 2
• Persistent nasal crusting and bleeding, especially if patient feels disproportionately unwell 2

Consider Testing In

• Autoimmune hepatitis type 1 without conventional autoantibodies 6
• Diagnostic uncertainty between ulcerative colitis and Crohn's disease 6
• Sinonasal symptoms with septal perforation, persistent bleeding, and obstruction 2

Critical Clinical Correlations

MPO-ANCA Positive Phenotype

• Glomerulonephritis 2, 3
• Peripheral neuropathy 2, 3
• Purpura 2, 3
• Lower risk of pulmonary infiltrates and cardiac manifestations 2
• Significantly lower relapse rates compared to PR3-ANCA patients 1

PR3-ANCA Positive Phenotype (in EGPA)

• Lung nodules 2
• Skin manifestations 2
• Less frequent active asthma 2
• Less frequent peripheral neuropathy 2
• Less frequent hypereosinophilia 2
• Phenotype closer to GPA 2

Diagnostic Pitfalls and False Positives

ANCA positivity alone never establishes the diagnosis—clinical context and confirmatory testing are essential. 5

Non-Vasculitic Causes of ANCA Positivity

• Infections: Including mycoplasma, which can trigger ANCA production leading to false positives 5
• Inflammatory bowel disease: Can show isolated P-ANCA positivity without MPO specificity 2
• Autoimmune liver disease 2, 6
• Rheumatoid arthritis 2
• Drug-induced vasculitis: Particularly cocaine adulterated with levamisole 2
• Cystic fibrosis: 80% show atypical c-ANCA with BPI as target antigen 2

Distinguishing True Vasculitis from False Positives

• Multi-organ involvement suggests true vasculitis 5
• Characteristic histopathology (granulomatous inflammation, necrosis, vasculitis) on biopsy confirms vasculitis 5
• Persistent ANCA positivity after infection treatment indicates true vasculitis 5
• Specific antigen testing (MPO vs PR3) improves specificity over IIF patterns alone 5

Immediate Actions When ANCA is Positive

For organ-threatening disease, initiate remission induction therapy with rituximab or cyclophosphamide plus high-dose glucocorticoids immediately without waiting for biopsy confirmation. 1

Urgent Assessments Required

• Urinalysis with microscopy for dysmorphic RBCs and red cell casts 1
• Renal function (GFR) 1
• Chest imaging for pulmonary involvement 1
• ESR and CRP 1
• Consider tissue biopsy (kidney biopsy has 91.5% diagnostic yield in GPA) 1

Prognostic Implications

• ANCA-negative patients (in EGPA) have worse overall survival, likely due to higher frequency of cardiac involvement 2
• ANCA-positive patients tend to have more frequent relapses 2, 3
• Sequential ANCA monitoring can be useful in predicting relapse in some patients, though not all show classical fluctuation with disease activity 2, 5
• ANCA status itself does not guide treatment choice 2