Umbilical cord blood levels of maternal antibodies reactive with p200 and full‐length Ro 52 in the assessment of risk for cardiac manifestations of neonatal lupus

Abstract

Objective Maternal anti-Ro autoantibodies associate with cardiac manifestations of neonatal lupus (cardiac NL), yet only 2% of women with this reactivity have an affected child. Identification of a more specific marker would channel intense monitoring to fetuses at greater risk. This study aims to determine whether autoantibodies against Ro52 amino acids 200–239 (p200) confer added risk over autoantibodies to full length Ro52, Ro60 or La. Methods/Results Anti-Ro-exposed pregnancies resulting in cardiac NL or no cardiac manifestations were identified from the Research Registry for Neonatal Lupus and PR Interval and Dexamethasone Evaluation. Umbilical cord (n=123) and maternal (n=115) samples were evaluated by ELISA. The frequencies of p200, Ro52, Ro60 and La autoantibodies were not significantly different between affected and unaffected children. However, neonatal anti-Ro52 and Ro60 titers were highest in cardiac NL and their unaffected siblings compared to unaffected neonates without a cardiac NL sibling. Although both maternal anti-Ro52 and p200 autoantibodies were less than 50% specific for cardiac NL, anti-p200 was the least likely of the Ro autoantibodies to be false positive in mothers who have never had an affected child. Titers of anti-Ro52 and p200 did not differ during a cardiac NL or unaffected pregnancy from the same mother. Conclusion Maternal reactivity to p200 does not confer an added risk to fetal conduction defects over full length Ro52 or Ro60 autoantibodies. Mothers who may never be at risk for having an affected child have lower anti-Ro60 titers and may require less stringent echocardiographic monitoring compared to women with high titer autoantibodies.

Modulation of natural IgM autoantibodies to oxidative stress-related neo-epitopes on apoptotic cells in newborns of mothers with anti-Ro autoimmunity

“…103 plasma samples were obtained from the umbilical cords of newborns of autoimmune mothers enrolled in the NYU IRB approved Research Registry for Neonatal Lupus (NL), as previously described [27, 36]. Enrollment of a pregnant subject required seropositivity for anti-Ro (Ro52 and/or Ro60) and/or anti-La48 and/or anti-RNP IgG-antibodies by clinical laboratory testing, with later confirmation in our research laboratory, as described [36].…”

“…Enrollment of a pregnant subject required seropositivity for anti-Ro (Ro52 and/or Ro60) and/or anti-La48 and/or anti-RNP IgG-antibodies by clinical laboratory testing, with later confirmation in our research laboratory, as described [36]. All mothers in the registry provided informed consent.…”

Neonatal Lupus

“…Joanne Reed and colleagues addressed some of these limitations by assessing umbilical blood from both affected and unaffected siblings, or simultaneously evaluating maternal and neonatal sera for anti-Ro60, anti-Ro52, anti-p200, and anti-La antibodies [ 82 ]. They noted that the presence of both anti-Ro52 and p200 antibodies was more common in mothers pregnant with a child with cardiac-NL or who had a previous child with cardiac-NL compared to mothers who never had a child with cardiac-NL.…”

“…They noted that the presence of both anti-Ro52 and p200 antibodies was more common in mothers pregnant with a child with cardiac-NL or who had a previous child with cardiac-NL compared to mothers who never had a child with cardiac-NL. However, both anti-Ro52 and p200 autoantibodies were of low specifi city for cardiac-NL [ 82 ]. Based on the 2 % prevalence of cardiac-NL in anti-Ro60 positive mothers [ 14 -17 ], the presence of anti-Ro52 and antip200 minimally increases the risk of cardiac-NL to 2.2 and 2.6 %, respectively [ 82 ].…”

“…Based on the 2 % prevalence of cardiac-NL in anti-Ro60 positive mothers [ 14 -17 ], the presence of anti-Ro52 and antip200 minimally increases the risk of cardiac-NL to 2.2 and 2.6 %, respectively [ 82 ]. Overall the presence of p200 antibodies was common in each group, suggesting that p200 is a dominant epitope in the anti-Ro52 response regardless of fetal outcome [ 82 ].…”