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Journal Article
Review
Does infection play a role in the pathogenesis of pulmonary vasculitis?
Seminars in Respiratory Infections 2003 March
The pulmonary vasculitides are a heterogeneous group of systemic inflammatory diseases of unknown etiology with potential for significant morbidity. The syndromes with particular predilection for the respiratory tract are Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. The discovery of antineutrophil cytoplasmic antibodies (ANCA) in these disorders has facilitated their diagnosis and contributed to the understanding of their pathogenesis. Clinical studies and some animal models suggest a disease-modifying role for antimicrobial therapy in ANCA-associated vasculitis. Nasal colonization with Staphylococcal aureus is an independent risk factor for relapse of Wegener's granulomatosis. This evidence suggests infectious pathogens as potential triggers of a cascade of events that result in vascular inflammation. Multiple laboratory studies have contributed to a coherent and plausible theory about the pathogenesis of ANCA-associated vasculitis in which infection plays a critical role. In susceptible individuals immune tolerance may break down and ANCA production resulting from molecular mimicry ensues. In addition, bacterial superantigens may serve as potent stimulators of the immune system. In this context, ANCA directed against proteinase 3 or myeloperoxidase may interact with their target antigens expressed on the surface of activated neutrophils, leading to an enhanced and perpetuated inflammation of vessels. Despite significant advances, the precise connection between infections and pulmonary vasculitis remains poorly understood, and further studies into the pathogenesis of these diseases are needed.
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