The environment, geoepidemiology and ANCA-associated vasculitides

Abstract

Anti-neutrophil cytoplasmic antibodies, directed against constituents of granules of neutrophils and lysosomes of monocytes, are serological markers of small vessel vasculitides, including Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and renal-limited vasculitis. These vasculitides are collectively termed ANCA-associated vasculitides (AAV). Environmental factors have been considered important in the development of ANCA, including silica, infection especially with Staphylococcus aureus, and drugs. Accelerated apoptosis of neutrophils induced through intratracheal instillation of silica may act as a trigger in the development of AAV. Inhaled silica may activate alveolar macrophages and not only induce inflammation and activation of fibroblasts, but also stimulate lymphocytes through T-cell receptors and attract neutrophils. Staphylococcus aureus is associated with initiation and relapse of Wegener's granulomatosis. Peptides from complementary PR3 show strong homology with peptides from S. aureus, which could underlie the development of PR3-ANCA. There is increasing recognition that drugs, especially propylthiouracil (PTU), may cause AAV. Patients with PTU-induced AAV have better prognosis than those with primary AAV. The disease spectrum of AAV in various geographic regions is different, which may suggest that the initiating factor in AAV has a different geographical distribution. Differences in genetic background may also be important in determining the response to triggering or initiating factors.