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Reactivity to the p305 Epitope of the α1G T-Type Calcium Channel and Autoimmune-Associated Congenital Heart Block.

Authors :
Markham AJ
Rasmussen SE
Salmon JE
Martinez-Ortiz W
Cardozo TJ
Clancy RM
Buyon JP
Source :
Journal of the American Heart Association [J Am Heart Assoc] 2015 May 20; Vol. 4 (5). Date of Electronic Publication: 2015 May 20.
Publication Year :
2015

Abstract

Background: Only 2% of mothers positive for anti-SSA/Ro (Ro) antibodies have children with congenital heart block (CHB). This study aimed to determine whether reactivity with p305, an epitope within the α1G T-type calcium channel, confers added risk over anti-Ro antibodies.<br />Methods and Results: Using sera from anti-Ro-exposed pregnancies resulting in offspring with CHB, no disease but CHB-sibling, and no disease and no CHB-sibling, as well as disease (lupus without anti-Ro) and healthy controls, reactivities were determined for binding to Ro60, p305, and an epitope within Ro60, p133-Ro60, which shares structural properties with p305, including key amino acids and an α-helical structure. Candidate peptides were further evaluated in an in vitro model that assessed the binding of maternal antibodies to apoptotic cells. In anti-Ro-positive mothers, anti-p305 autoantibodies (>3 SD above healthy controls) were detected in 3/59 (5%) CHB pregnancies, 4/30 (13%) unaffected pregnancies with a CHB-sibling, and 0/42 (0%) of unaffected pregnancies with no CHB-sibling. For umbilical bloods (61 CHB, 41 healthy with CHB sibling), no association of anti-p305 with outcome was detected; however, overall levels of anti-p305 were elevated compared to mothers during pregnancy in all groups studied. For anti-p133-Ro60, reactivity paralleled that of anti-p305. In the screen employing apoptotic cells, p133-Ro60, but not p305, significantly attenuated the binding of immunoglobulin G isolated from a mother whose child had CHB (42.1% reduced to 13.9%, absence/presence of p133-Ro60, respectively, P<0.05).<br />Conclusions: These data suggest that anti-p305 is not a robust maternal marker for assessing increased risk of CHB during an anti-SSA/Ro pregnancy.<br /> (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Details

Language :
English
ISSN :
2047-9980
Volume :
4
Issue :
5
Database :
MEDLINE
Journal :
Journal of the American Heart Association
Publication Type :
Academic Journal
Accession number :
25994441
Full Text :
https://doi.org/10.1161/JAHA.115.001836