Which serum marker is most specific for the diagnosis of granulomatosis with polyangiitis (GPA)?

Explanation

## ANCA Patterns in Vasculitis — Diagnostic Specificity **Key Point:** c-ANCA (cytoplasmic ANCA) with anti-PR3 (proteinase-3) antibodies is the most specific serum marker for GPA, present in 90% of generalized GPA cases. ### ANCA Patterns and Associated Vasculitides | ANCA Pattern | Target Antigen | Associated Vasculitis | Frequency in Disease | Specificity | |---|---|---|---|---| | **c-ANCA** | **PR3** | **GPA** | **90% (generalized)** | **95–99%** | | p-ANCA | MPO | MPA, EGPA | 80% (MPA), 40% (EGPA) | 85–90% | | p-ANCA | MPO | Drug-induced ANCA vasculitis | Variable | Lower | | — | GBM | Anti-GBM disease | 100% | 100% but different disease | | — | ESR elevation | Non-specific inflammation | Multiple conditions | Very low | **High-Yield:** **c-ANCA/PR3 = GPA** is the most frequently tested ANCA association in NEET PG. The presence of c-ANCA with anti-PR3 in a patient with upper respiratory, pulmonary, and/or renal involvement is virtually diagnostic of GPA. **Clinical Pearl:** Approximately 10% of GPA patients are ANCA-negative (seronegative GPA), so a negative ANCA does NOT exclude GPA if clinical suspicion is high. However, when ANCA is positive, c-ANCA/PR3 is the hallmark. **Mnemonic:** **c-ANCA = cytoplasmic = GPA; p-ANCA = perinuclear = MPA/EGPA** ### Why c-ANCA/PR3 Is Most Specific - PR3 is a neutrophil serine protease found in azurophilic granules - Anti-PR3 antibodies activate neutrophils and cause necrotizing inflammation - The combination of c-ANCA pattern + anti-PR3 positivity has >95% specificity for GPA - This is superior to clinical features alone and to other serologic markers