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

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.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. © 2015 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.