β 2-glycoprotein I and protection from anti-SSA/Ro60- associated cardiac manifestations of neonatal lupus

Joanne Reed, Robert Clancy, A Purcell, Mimi Kim, Thomas Gordon

    Research output: Contribution to journalArticle

    24 Citations (Scopus)

    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 β2-glycoprotein I (β2GPI) 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 β2GPI and maternal anti-Ro60 Abs for binding apoptotic induced surface-translocated Ro60 occurs on human fetal cardiomyocytes; and 2) circulating levels of β2GPI influence injury in anti-Ro60-exposed fetuses. Initial flow cytometry experiments conducted on apoptotic human fetal cardiomyocytes demonstrated dose-dependent binding of β2GPI. In competitive inhibition experiments, β2GPI prevented opsonization of apoptotic cardiomyocytes by maternal anti-Ro60 IgG. ELISA was used to quantify β2GPI in umbilical cord blood from 97 neonates exposed to anti-Ro60 Abs, 53 with cardiac NL and 44 with no cardiac disease. β2GPI levels were significantly lower in neonates with cardiac NL. Plasmin-mediated cleavage of β2GPI prevented binding to Ro60 and promoted the formation of pathogenic anti-Ro60 IgG-apoptotic cardiomyocyte complexes. In aggregate these data suggest that intact β2GPI in the fetal circulation may be a novel cardioprotective factor in anti-Ro60-exposed pregnancies.

    Original languageEnglish
    Pages (from-to)520-526
    Number of pages7
    JournalJournal of Immunology
    Volume187
    Issue number1
    DOIs
    Publication statusPublished - 1 Jul 2011

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