title: Reactivity to the p305 Epitope of the α1G T-Type Calcium Channel and Autoimmune-Associated Congenital Heart Block.
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.
  
  
  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.
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, NY (A.J.M., S.E.R., R.M.C., J.P.B.).
authors.forename: Androo J
authors.initials: AJ
authors.lastname: Markham
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, NY (A.J.M., S.E.R., R.M.C., J.P.B.).
authors.forename: Sara E
authors.initials: SE
authors.lastname: Rasmussen
authors.affiliation: Division of Rheumatology, Hospital for Special Surgery, New York, NY (J.E.S.).
authors.forename: Jane E
authors.initials: JE
authors.lastname: Salmon
authors.affiliation: Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY (W.M.O., T.J.C.).
authors.forename: Wilnelly
authors.initials: W
authors.lastname: Martinez-Ortiz
authors.affiliation: Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY (W.M.O., T.J.C.).
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Cardozo
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, NY (A.J.M., S.E.R., R.M.C., J.P.B.).
authors.forename: Robert M
authors.initials: RM
authors.lastname: Clancy
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, NY (A.J.M., S.E.R., R.M.C., J.P.B.).
authors.forename: Jill P
authors.initials: JP
authors.lastname: Buyon
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D020747:Calcium Channels, T-Type / Q000097:blood / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000097:blood / Q000276:immunology; D005260:Female; D006327:Heart Block / Q000097:blood / Q000151:congenital* / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D015415:Biomarkers; D020747:Calcium Channels, T-Type; D000939:Epitopes; C035356:SS-A antibodies
keywords: apoptosis; heart block; risk factors