Paper II
Question
Antineutrophil cytoplasmic antibodies
Answer
Antineutrophil cytoplasmic antibodies (ANCAs) are autoantibodies directed against constituents of neutrophil cytoplasmic granules, important in the diagnosis and pathogenesis of certain small-vessel vasculitides.
Types
- c-ANCA (cytoplasmic pattern): Directed against proteinase-3 (PR3) — strongly associated with granulomatosis with polyangiitis (Wegener granulomatosis)
- p-ANCA (perinuclear pattern): Directed against myeloperoxidase (MPO) — associated with microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
Pathogenic mechanism
- ANCAs bind to their target antigens on the surface of cytokine-primed neutrophils, causing premature activation and degranulation
- Activated neutrophils adhere to and damage vascular endothelium, releasing reactive oxygen species and proteolytic enzymes, producing necrotizing vasculitis of small vessels
Clinical utility
- Serve as important diagnostic markers and can be used to monitor disease activity/response to treatment in ANCA-associated vasculitides