title: β2-glycoprotein I and protection from anti-SSA/Ro60-associated cardiac manifestations of neonatal lupus.
abstract: One mechanism to molecularly explain the strong association of maternal anti-Ro60 Abs with cardiac disease in neonatal lupus (NL) is that these Abs initiate injury by binding to apoptotic cardiomyocytes in the fetal heart. Previous studies have demonstrated that β(2)-glycoprotein I (β(2)GPI) interacts with Ro60 on the surface of apoptotic Jurkat cells and prevents binding of anti-Ro60 IgG. Accordingly, the current study was initiated to test two complementary hypotheses, as follows: 1) competition between β(2)GPI and maternal anti-Ro60 Abs for binding apoptotic induced surface-translocated Ro60 occurs on human fetal cardiomyocytes; and 2) circulating levels of β(2)GPI influence injury in anti-Ro60-exposed fetuses. Initial flow cytometry experiments conducted on apoptotic human fetal cardiomyocytes demonstrated dose-dependent binding of β(2)GPI. In competitive inhibition experiments, β(2)GPI prevented opsonization of apoptotic cardiomyocytes by maternal anti-Ro60 IgG. ELISA was used to quantify β(2)GPI in umbilical cord blood from 97 neonates exposed to anti-Ro60 Abs, 53 with cardiac NL and 44 with no cardiac disease. β(2)GPI levels were significantly lower in neonates with cardiac NL. Plasmin-mediated cleavage of β(2)GPI prevented binding to Ro60 and promoted the formation of pathogenic anti-Ro60 IgG-apoptotic cardiomyocyte complexes. In aggregate these data suggest that intact β(2)GPI in the fetal circulation may be a novel cardioprotective factor in anti-Ro60-exposed pregnancies.
authors: Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA. joanne.reed@nyumc.org
authors: Joanne H
authors: JH
authors: Reed
authors: Robert M
authors: RM
authors: Clancy
authors: Anthony W
authors: AW
authors: Purcell
authors: Mimi Y
authors: MY
authors: Kim
authors: Tom P
authors: TP
authors: Gordon
authors: Jill P
authors: JP
authors: Buyon
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