Which of the following correctly describes the pathophysiology of PR3-ANCA (c-ANCA) in granulomatosis with polyangiitis (GPA)?

• A PR3-ANCA activates the classical complement pathway causing MAC-mediated vessel wall destruction
• B PR3-ANCA induces T-cell-mediated granuloma formation via Th17 pathway independently of neutrophil activation
• C PR3-ANCA acts as blocking antibody to VEGF, impairing endothelial repair
• D PR3-ANCA binds to primed neutrophil surface PR3, triggering degranulation, superoxide burst, and endothelial damage via direct cytotoxicity ✓

Explanation

In ANCA-associated vasculitis, cytokines (particularly TNF-α and IL-8 from infection or inflammation) prime neutrophils, causing PR3 and MPO to translocate to the cell surface. Circulating ANCA (IgG) binds these surface antigens, causing Fc-receptor-mediated neutrophil activation, degranulation, and respiratory burst. The released proteases and reactive oxygen species damage small vessel endothelium, leading to pauci-immune necrotising vasculitis (pauci-immune = little/no immunoglobulin on biopsy). Complement activation is not the primary pathway. T-cells and granuloma formation co-exist but are downstream events, not the initiating mechanism.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.