Affiliation:
1. Department of Medicine, New York University School of Medicine, New York, NY
2. Division of Rheumatology, Hospital for Special Surgery, New York, NY
3. Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY
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 α
1G
T‐type calcium channel, confers added risk over anti‐Ro antibodies.
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).
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
8 articles.
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