Anti-Neutrophil Cytoplasmic Antibodies—Cytoplasmic Pattern (c-ANCA)

c-ANCA are autoantibodies directed against cytoplasmic components of neutrophils—most commonly proteinase 3 (PR3). They are hallmark markers for certain small-vessel vasculitides, particularly:

• Granulomatosis with Polyangiitis (GPA) (formerly Wegener’s granulomatosis)
• Microscopic Polyangiitis (MPA)

Pathophysiology

1. Targeting: c-ANCA bind to PR3 within neutrophils.
2. Activation: Bound neutrophils become inappropriately activated and adhere to vessel walls.
3. Inflammation: Release of lytic enzymes and reactive oxygen species damages blood vessel endothelium.

Clinical Features

• Constitutional: Fatigue, fever, weight loss
• Musculoskeletal: Arthralgia, myalgia
• Dermatologic: Purpura, ulcers, nodules
• Respiratory: Sinusitis, nasal crusting, hemoptysis, pulmonary nodules or hemorrhage
• Renal: Hematuria, proteinuria, rapidly progressive glomerulonephritis

Diagnosis

1. Indirect Immunofluorescence (IIF): A cytoplasmic staining pattern (“c-ANCA”) on ethanol-fixed neutrophils.
2. ELISA: Quantitative measurement of anti-PR3 antibodies confirms specificity.
3. Tissue Biopsy (if needed): Confirms necrotizing granulomatous inflammation in GPA or pauci-immune vasculitis in MPA.

Management

• Immunosuppression: High-dose corticosteroids combined with cyclophosphamide, rituximab, or methotrexate to induce remission.
• Maintenance Therapy: Lower-dose immunosuppressants (azathioprine, methotrexate) to prevent relapse.
• Monitoring: Regular c-ANCA titres, renal function, and imaging as indicated.

Frequently Asked Questions

1. What is c-ANCA?
   Autoantibodies against neutrophil cytoplasmic antigens (PR3) associated with vasculitis.
2. How is c-ANCA tested?
   By IIF (cytoplasmic pattern) and confirmed by ELISA for anti-PR3.
3. Which diseases are linked to c-ANCA?
   Primarily GPA and MPA, both forms of small-vessel vasculitis.
4. Can c-ANCA levels fluctuate?
   Yes—titres often correlate with disease activity and can be used for monitoring.
5. Is there a cure for c-ANCA-associated vasculitis?
   No definitive cure, but immunosuppressive therapy can induce and maintain remission.