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SP0149 Endothelial Damage in Anca-Associated Vasculitis (AAV)
  1. C. Kallenberg
  1. Dept. of Rheumatology & Clinical Immunology, University Medical Center Groningen, Groningen, Netherlands


The AAV are characterized by necrotizing vasculitis of small and medium-sized blood vessels in conjunction with the presence of autantibodies directed to proteinase-3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The kidneys are frequently involved with fibrinoid necrosis and paucity of immune deposits. In vitro studies show that primed neutrophils can be activated by ANCA to produce reactive oxygen species and release lytic enzymes. Together with monolayers of endothelial cells this leads to endothelial damage. In an in vitro flow system ANCA stabilize adhesion and promote migration of neutrophils on endothelial cells. In vivo models of MPO-ANCA vasculitis show the pathogenic potential of MPO-ANCA to induce necrotizing glomerulonephritis and pulmonary capillaritis. Also in vivo MPO-ANCA augments leukocyte-microvascular interactions resulting in microvascular injury. In these models as well as in human AAV the complement system plays a major role, in particular the alternative pathway of complement activation and the strong chemo-attractive degranulation product C5a. Also PR3-ANCA appears able, in an animal model, to induce necrotizing vasculitis, although less clear than MPO-ANCA. Cellular immunity may be involved as well in AAV, particularly in PR3-ANCA associated disease. CD4-positive T-cells expressing NKG2D are increased in PR3-ANCA disease in conjunction with increased levels of IL-15, a pro-inflammatory cytokine that, amongst others, induces expression of NKG2D on CD4-positive T-cells enabling these cells to interact with MIC-A/MIC-B on endothelial cells resulting in damage of the latter cells.

In conclusion, ANCA are able to induce endothelial damage in AAV but an additional role of T-cells is suggested as well.

Ref.: Kallenberg et al, Am J Kidney Dis 2013;62:1176-87

Disclosure of Interest None declared

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