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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.

Elevated soluble Flt1 mediates an anti-angiogenic state in patients with ANCA-associated vasculitis