Physiopathologie des vascularites ANCA-positives

Key points ANCA-associated vasculitides comprise granulomatosis with polyangiitis (GPA) (formerly names Wegener's granulomatosis), Churg-Strauss syndrome (SCS) (which will be renamed GPA and eosinophilia) and microscopic polyangiitis (MPA) . Immune cells (dendritic and non dendritic cells) and inflammatory cells (neutrophils, monocytes, macrophages) and resident cells (endothelial cells, fibroblasts) are implicated in the pathophysiology of ANCA-associated vasculitides. One of the targets of ANCA, myeloperoxydase, is only present in the azurophil granules of neutrophils , whereas the other target of these antibodies, proteinase 3, is also present at the internal face of cytoplasmic membrane of neutrophils, as well as at their surface. Anti-myeloperoxydase ANCA are pathogenic in vitro and in vivo, whereas the pathogenicity of anti-proteinase 3 ANCA has only been demonstrated in vitro and recent studies suggest a pathogenic role of ANCA anti-PR3 in mouse model. Two phenotypes of GPA can be distinguished: a granulomatous form, localized to the respiratory tract with Th1 immune response features, and a vasculitic form with Th2 immune response features . Recently, an increase in TH17 lymphocytes at the acute phase and a defect in T regulatory cells at the chronic phase have been identified in GPA. The role of B-lymphocytes in the pathogenesis of ANCA-associated vasculitides is now well documented by the effectiveness of rituximab in the treatment of this condition.