The role of alpha1 -antitrypsin Deficiency in the Pathogenesis of Antineutrophil Cytoplasmic Antibodies Associated Systemic Necrotizing Vasculitides.

Alpha1-antitrypsin (D,1AT) is the most abundant circulating protease inhibitor (Pi) in human plasma. It has central function in controlling tissue degradation by inhibiting a large number of proteases including neutrophil elastase and proteinase 3 (PR3). PR3, the Wegner's autoantigen, has been suggested to be involved in the pathogenesis of small-vessel systemic vasculitides. alpha1 AT deficiency (PiZ) is frequent in Caucasian populations, and its homozygous state (PiZZ) is known to predispose to lung emphysema and chronic liver disease. A strong correlation between heterozygous (PiZ) and homozygous (PiZZ) alpha1 AT deficiency and anti-neutrophil cytoplasmic autoantibodies (ANCA) associated systemic nocrotizing vasculitides has recently been reported in various populations. In this review the pathogenesis of small-vessel vasculitides is outlined, focusing on the role of alpha1 AT deficiency. alpha1 AT has been suggested to have a crucial role as a protective protein in ANCA-associated vasculitic syndromes.