Pathophysiology of Microscopic Polyangiitis

Core Autoimmune Mechanism

The American College of Rheumatology suggests that microscopic polyangiitis (MPA) is an autoimmune small-vessel vasculitis driven primarily by anti-myeloperoxidase (MPO) ANCA antibodies that activate neutrophils, causing necrotizing inflammation of capillaries, venules, and arterioles without granuloma formation 1, 2
The pathogenic cascade begins with autoantibody formation against myeloperoxidase (MPO), a neutrophil enzyme normally sequestered in primary granules, as stated by the European League Against Rheumatism 2, 3

The activation of neutrophils by MPO-ANCA antibodies triggers a destructive inflammatory cascade, according to the British Society for Rheumatology 1, 2
ANCA binding to neutrophils causes release of oxygen radicals, lytic enzymes, and inflammatory cytokines that directly damage vessel walls, as reported by the American Academy of Otolaryngology 4, 5

Understanding that MPA is primarily MPO-ANCA driven has direct clinical relevance for diagnosis and monitoring, as stated by the American College of Physicians 1, 2
ANCA-negative MPA exists and presents a diagnostic challenge, as the pathophysiology in these cases may involve alternative mechanisms not yet fully elucidated, according to the European Respiratory Society 6, 4
Patients with MPA are typically older at presentation and have more severe kidney disease compared to GPA patients, reflecting the predilection for renal capillary involvement, as reported by the National Kidney Foundation 1, 2
The pathogenic role of MPO-ANCA is supported by both in vitro studies showing direct neutrophil activation and endothelial damage, and clinical evidence that B-cell depletion (rituximab) effectively treats disease by reducing antibody production, as stated by the American College of Rheumatology 7