Pathophysiology
Clinical meaning
Microscopic polyangiitis (MPA) is an ANCA-associated small-vessel vasculitis characterized by necrotizing inflammation of capillaries, venules, and arterioles without granulomatous inflammation โ this absence of granuloma formation is the key histopathological distinction from granulomatosis with polyangiitis (GPA/Wegener). MPA is strongly associated with perinuclear ANCA (p-ANCA) directed against myeloperoxidase (MPO-ANCA, positive in 80-90% of cases). The pathogenesis begins with neutrophil priming by pro-inflammatory cytokines (TNF-alpha, complement factor C5a) that cause MPO to translocate from azurophilic granules to the neutrophil cell surface. Circulating MPO-ANCA antibodies then bind surface-expressed MPO, activating neutrophils through Fc-gamma receptor crosslinking and direct F(ab')2-mediated signaling, triggering degranulation and release of reactive oxygen species, proteolytic enzymes (elastase, proteinase 3), and neutrophil extracellular traps (NETs) that directly damage the endothelium of small vessels. Activated neutrophils also adhere firmly to endothelial cells via beta-2 integrin interactions, concentrating their destructive cargo at the vessel wall and producing fibrinoid necrosis. The hallmark clinical presentation is the pulmonary-renal syndrome: rapidly progressive glomerulonephritis (RPGN) presenting as hematuria with red blood cell casts, proteinuria, and rapidly rising serum creatinine โ the renal biopsy shows pauci-immune crescentic glomerulonephritis...