β2-glycoprotein I and protection from anti-SSA/Ro60- associated cardiac manifestations of neonatal lupus

Joanne H. Reed, Robert M. Clancy, Anthony W. Purcell, Mimi Kim, Tom P. Gordon, Jill P. Buyon

Research output: Contribution to journalArticle

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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 (US)
Pages (from-to)520-526
Number of pages7
JournalJournal of Immunology
Volume187
Issue number1
DOIs
StatePublished - Jul 1 2011

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Glycoproteins
Cardiac Myocytes
Mothers
Heart Diseases
Neonatal Systemic lupus erythematosus
Fetal Heart
Jurkat Cells
Fibrinolysin
Wounds and Injuries
Fetal Blood
Flow Cytometry
Fetus
Enzyme-Linked Immunosorbent Assay
Pregnancy
anti-IgG

ASJC Scopus subject areas

  • Immunology

Cite this

β2-glycoprotein I and protection from anti-SSA/Ro60- associated cardiac manifestations of neonatal lupus. / Reed, Joanne H.; Clancy, Robert M.; Purcell, Anthony W.; Kim, Mimi; Gordon, Tom P.; Buyon, Jill P.

In: Journal of Immunology, Vol. 187, No. 1, 01.07.2011, p. 520-526.

Research output: Contribution to journalArticle

Reed, Joanne H. ; Clancy, Robert M. ; Purcell, Anthony W. ; Kim, Mimi ; Gordon, Tom P. ; Buyon, Jill P. / β2-glycoprotein I and protection from anti-SSA/Ro60- associated cardiac manifestations of neonatal lupus. In: Journal of Immunology. 2011 ; Vol. 187, No. 1. pp. 520-526.
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