Abstract
Serum levels of soluble Flt1 (sFlt1), a potent inhibitor of VEGF, are significantly increased during the acute phase of PR3-AAV (2592 ± 11347 pg/ml) and MPO-AAV (476 ± 4258 pg/ml) compared to controls (118 ± 269 pg/ml). sFlt1 levels decreased during disease remission but remained increased compared to controls in patients with PR3-AAV. sFlt1 serum levels correlated with serum levels of C5a, an anaphylatoxin released following complement activation. Serum from patients with acute PR3-AAV induced the release of sFlt1 by human monocytes in vitro, but failed to induce a similar effect on endothelial cells. Pre-treatment of monocytes with an anti-C5a receptor blocking antibody attenuated sFlt1 release. Serum from patients with acute AAV induced a disruption of blood flow in the chicken chorioallantoic membrane assay and this effect was prevented by incubating patients’ serum with an excess of human VEGF.
Highlights
Anti-neutrophil cytoplasm antibody-associated vasculitidies (AAV) represent a group of necrotizing small vessel vasculitidies that include Wegener’s granulomatosis, microscopic polyangiitis and Churg-Strauss-Syndrome
Elevated soluble Flt1 mediates an anti-angiogenic state in patients with ANCA-associated vasculitis
Serum levels of soluble Flt1, a potent inhibitor of vascular endothelial growth factor (VEGF), are significantly increased during the acute phase of PR3-AAV (2592 ± 11347 pg/ml) and MPO-AAV (476 ± 4258 pg/ml) compared to controls (118 ± 269 pg/ml). sFlt1 levels decreased during disease remission but remained increased compared to controls in patients with PR3-AAV. sFlt1 serum levels correlated with serum levels of C5a, an anaphylatoxin released following complement activation
Summary
S Le Roux1,2,3†, R Pepper4†, A Dufay, M Néel, N Lamandé, M Rimbert, R Josien, M Hamidou, M Hourmant, H T Cook, B Charreau, E Larger, A Salama4*, F Fakhouri1,2,3*. From 5th European Workshop on Immune-Mediated Inflammatory Diseases Sitges-Barcelona, Spain. From 5th European Workshop on Immune-Mediated Inflammatory Diseases Sitges-Barcelona, Spain. 1-3 December 2010
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