DigiFab interacts with endogenous cardiotonic steroids and reverses preeclampsia-induced Na/K-ATPase inhibition.

Elevated levels of endogenous Na/K-ATPase (NKA) inhibitors, cardiotonic steroids (CTSs) including marinobufagenin (MBG), contribute to pathogenesis of preeclampsia (PE) and represent a target for immunoneutralization by Digibind (Ovine Digoxin Immune Antibody, Glaxo-Smith Kline). Because Digibind is no longer commercially available, we studied whether DigiFab (BTG International Ltd, UK) can substitute Digibind for immunoneutralization of CTS in patients with PE. We compared DigiFab, Digibind, and anti-MBG monoclonal antibody (mAb) with respect to their ability to interact with CTS in PE plasma and to restore NKA activity in erythrocytes from patients with PE.

Interaction of Digibind with endogenous cardiotonic steroids from preeclamptic placentae.

Background: Preeclampsia is a major cause of maternal and fetal mortality, and its pathogenesis is not fully understood. Endogenous digitalis-like cardiotonic steroids (CTS) have been implicated in the pathophysiology of preeclampsia; this is illustrated by clinical observations that Digibind, a therapeutic digoxin antibody fragment which binds CTS, lowers blood pressure and reverses Na/K-ATPase inhibition in patients with preeclampsia. Recently we reported that plasma levels of marinobufagenin (MBG), a bufadienolide vasoconstrictor CTS, are increased four-fold in patients with severe preeclampsia.