Linked Life Data

21602492

Source:http://linkedlifedata.com/resource/pubmed/id/21602492

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-6-21
pubmed:abstractText
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 ?(2)-glycoprotein I (?(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 ?(2)GPI and maternal anti-Ro60 Abs for binding apoptotic induced surface-translocated Ro60 occurs on human fetal cardiomyocytes; and 2) circulating levels of ?(2)GPI influence injury in anti-Ro60-exposed fetuses. Initial flow cytometry experiments conducted on apoptotic human fetal cardiomyocytes demonstrated dose-dependent binding of ?(2)GPI. In competitive inhibition experiments, ?(2)GPI prevented opsonization of apoptotic cardiomyocytes by maternal anti-Ro60 IgG. ELISA was used to quantify ?(2)GPI in umbilical cord blood from 97 neonates exposed to anti-Ro60 Abs, 53 with cardiac NL and 44 with no cardiac disease. ?(2)GPI levels were significantly lower in neonates with cardiac NL. Plasmin-mediated cleavage of ?(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 ?(2)GPI in the fetal circulation may be a novel cardioprotective factor in anti-Ro60-exposed pregnancies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
187
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
520-6
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:21602492-Antibodies, Antinuclear, pubmed-meshheading:21602492-Apoptosis, pubmed-meshheading:21602492-Autoantigens, pubmed-meshheading:21602492-Binding, Competitive, pubmed-meshheading:21602492-Cells, Cultured, pubmed-meshheading:21602492-Female, pubmed-meshheading:21602492-Fetal Blood, pubmed-meshheading:21602492-Fibrinolysin, pubmed-meshheading:21602492-Humans, pubmed-meshheading:21602492-Immunoglobulin G, pubmed-meshheading:21602492-Infant, Newborn, pubmed-meshheading:21602492-Jurkat Cells, pubmed-meshheading:21602492-Lupus Erythematosus, Systemic, pubmed-meshheading:21602492-Male, pubmed-meshheading:21602492-Myocytes, Cardiac, pubmed-meshheading:21602492-Protein Binding, pubmed-meshheading:21602492-RNA, Small Cytoplasmic, pubmed-meshheading:21602492-Ribonucleoproteins, pubmed-meshheading:21602492-beta 2-Glycoprotein I
pubmed:year
2011
pubmed:articleTitle
?2-glycoprotein I and protection from anti-SSA/Ro60-associated cardiac manifestations of neonatal lupus.
pubmed:affiliation
Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA. joanne.reed@nyumc.org
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Twin Study