Which antineutrophil cytoplasmic antibody (ANCA) pattern and target antigen are most commonly associated with granulomatosis with polyangiitis (Wegener granulomatosis)?

Explanation

## ANCA Patterns in Granulomatosis with Polyangiitis (GPA) **Key Point:** GPA is classically associated with **c-ANCA (cytoplasmic ANCA) targeting proteinase-3 (PR3)**, found in ~90% of generalized cases. ### ANCA Patterns and Target Antigens | ANCA Pattern | Immunofluorescence | Target Antigen | Associated Vasculitis | |---|---|---|---| | **c-ANCA** | Cytoplasmic, central | **PR3 (proteinase-3)** | **GPA (Wegener)** | | **p-ANCA** | Perinuclear, rim-like | **MPO (myeloperoxidase)** | **MPA, EGPA** | ### Pathophysiology - **PR3** is a serine protease present in neutrophil azurophilic granules - Anti-PR3 antibodies activate neutrophils → release of proteolytic enzymes → necrotizing vasculitis - **c-ANCA pattern** results from the cytoplasmic distribution of PR3 antigen **High-Yield:** - **GPA = c-ANCA/PR3** (remember: "GPA goes central") - **MPA/EGPA = p-ANCA/MPO** (remember: "perinuclear for peripheral vasculitis") **Mnemonic:** **CAGE** - **C**-ANCA → **G**ranulomatosis with **P**olyangiitis (GPA) - **P**-ANCA → **M**icroscopic **P**olyangiitis or **E**osinophilic **G**ranulomatosis with **P**olyangiitis (EGPA) **Clinical Pearl:** c-ANCA/PR3 positivity is found in ~90% of generalized GPA (with pulmonary and renal involvement) but only ~50% of limited disease (e.g., upper respiratory only).