Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis exhibits endothelial damage, but the capacity for vessel repair in this disorder is not well understood. Here, we observed a marked increase in serum levels of soluble Flt1 (sFlt1), a potent inhibitor of vascular endothelial growth factor, in patients with active ANCA-associated vasculitis compared with patients during remission and other controls. Serum levels of sFlt1 correlated with C5a, an anaphylatoxin released after complement activation. Serum from patients with acute ANCA-associated vasculitis disrupted blood flow in the chicken chorioallantoic membrane assay, suggesting an antiangiogenic effect. Preincubation with excess human vascular endothelial growth factor prevented this effect. Anti–proteinase-3 (PR3) mAb and serum containing PR3-ANCA from patients with active vasculitis both induced a significant and sustained release of sFlt1 from monocytes, whereas anti-myeloperoxidase (MPO) mAb or polyclonal antibodies did not. However, the serum containing polyclonal PR3-ANCA did not induce release of sFlt1 from cultured human umbilical vein endothelial cells. In summary, these data suggest that anti-PR3 antibodies, and to a much lesser extent anti-MPO antibodies, increase sFlt1 during acute ANCA-associated vasculitis, leading to an antiangiogenic state that hinders endothelial repair.

/pdf/elevated-soluble-flt1-inhibits-endothelial-repair-in-pr3-3vcyq0spau.pdf

Elevated Soluble Flt1 Inhibits Endothelial Repair in PR3-ANCA–Associated Vasculitis

Rituximab como terapia de mantenimiento en las vasculitis asociadas a ANCA: ¿cómo, cuándo y por qué?

Rituximab as maintenance therapy for ANCA associated vasculitis: how, when and why?

Rituximab en el tratamiento de las vasculitis asociadas a ANCA: ¿el futuro hoy?

............................................................................................................................................................... ii Table of

/pdf/the-health-resource-utilization-and-economic-burden-of-2sq25d5be0.pdf

The health resource utilization and economic burden of systemic autoimmune rheumatic diseases

Antineutrophil cytoplasmic autoantibody (ANCA)-associated systemic vasculitides (AASV) consists of small-vessel systemic inflammatory disorders which commonly affect the kidneys and without treatment have a poor prognosis. Rituximab is a novel biological agent which is being used experimentally in the management of AASV. This report presents the case of a young woman with rapidly progressive life-threatening AASV. Despite prompt diagnosis and initial treatment with steroids and alkylating agents her condition became life threatening. With addition of rituximab therapy she showed an excellent sustained response. Rituximab appears an effective and safe treatment choice for the induction of remission in severe AASV that is not responding to standard agents, at the initial presentation and for maintenance therapy, without the development of common serious side-effects associated with immunosuppression.

Rituximab for rescue and maintenance therapy in rapidly progressive life-threatening antineutrophil cytoplasmic autoantibody-associated systemic vasculitis

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Rituximab for rescue and maintenance therapy in rapidly progressive life-threatening antineutrophil cytoplasmic autoantibody-associated systemic vasculitis