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 are associated 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 aimed to determine whether autoantibodies against Ro 52 amino acids 200-239 (p200) confer added risk over autoantibodies to full-length Ro 52, Ro 60, or La.

Methods: Anti-Ro-exposed pregnancies resulting in cardiac NL or no cardiac manifestations were identified from the Research Registry for Neonatal Lupus and the PR Interval and Dexamethasone Evaluation study. Umbilical cord (n = 123) and maternal (n = 115) samples were evaluated by enzyme-linked immunosorbent assay.

Results: The frequencies of p200, Ro 52, Ro 60, and La autoantibodies were not significantly different between affected and unaffected children. However, neonatal anti-Ro 52 and Ro 60 titers were highest in cardiac NL and their unaffected siblings compared to unaffected neonates without a cardiac NL sibling. Although both maternal anti-Ro 52 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-Ro 52 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 Ro 52 or Ro 60 autoantibodies. Mothers who may never be at risk for having an affected child have lower anti-Ro 60 titers and may require less stringent echocardiographic monitoring compared to women with high-titer autoantibodies.

Copyright © 2012 by the American College of Rheumatology.

Figures

Figure 1. Umbilical cord blood titer of anti-p200, anti-Ro52, anti-Ro60 and anti-La

Reactivity of umbilical cord plasma from neonates with cardiac NL (Group 1), unaffected siblings of neonates with cardiac NL (Group 2), or unaffected neonates with only unaffected siblings (Group 3) against p200 (Ro52 aa 200–239) peptide (A), full length recombinant Ro52 (B), native Ro60 (C), or native La (D). The mean ELISA binding units of duplicate determinations is plotted for each neonate that was considered positive (>3 SD above the median binding units for 28 healthy controls). Cut-offs for positivity are >6.4 for Ro52, >4.5 for p200 and >19 for Ro60 and La. Solid lines represent the median ELISA binding units for each group.

Figure 2. Maternal serum titer of anti-p200, anti-Ro52, anti-Ro60 and anti-La

Reactivity of serum from mothers pregnant with a cardiac NL child (Group 1), an unaffected child born subsequent to a cardiac NL child (Group 2), or an unaffected child and had only unaffected children (Group 3) against p200 peptide (A) full length recombinant Ro52 (B), native Ro60 (C), or native La (D). The mean ELISA binding units of duplicate determinations is plotted for each neonate considered positive (>3 SD above the median binding units for 28 healthy controls). Cut-offs for positivity are >6.4 for Ro52, >4.5 for p200 and >19 for Ro60 and La. Solid lines represent the median ELISA binding units for each group.