Maternal antibody responses to the 52‐kd SSA/RO p200 peptide and the development of fetal conduction defects.

To identify a finer level of antibody specificity for risk of congenital heart block (CHB) than reactivity to 52‐kd SSA/Ro (Ro 52).Serum from mothers enrolled in the Research Registry for Neonatal Lupus and the observational PR Interval and Dexamethasone Evaluation (PRIDE) study was evaluated for reactivity against peptide aa200‐239 of Ro 52 (p200), recently reported to be associated with a higher risk of CHB.The majority of 156 Ro 52–positive sera tested were reactive with p200 (>3 SD above control), irrespective of the clinical status of the child. Optical density (OD) values of p200 did not differ significantly among mothers of children with CHB (mean ± SD 0.187 ± 0.363), mothers of children with rash (mean ± SD 0.176 ± 0.356), and mothers of children without neonatal lupus (mean ± SD 0.229 ± 0.315). Reactivity against p200 was found in 80 of 104 mothers of children with CHB (77%), 24 of 30 mothers of children with rash (80%), and 21 of 22 mothers who delivered healthy children and had no children with neonatal lupus (95%) (P not significant for all comparisons). Sera from 4 mothers of children with CHB with varied p200 titers (OD range 0.025–1.818) bound to the surface of nonpermeabilized apoptotic, but not proliferating, human fetal cardiocytes. In 32 Ro 52–positive women who completed the PRIDE study (22 with no child with neonatal lupus, 7 with a child with CHB, and 3 with a child with rash) in whom p200 levels were determined during pregnancy, the correlation between level of p200 (OD range 0.000–1.170) and maximal fetal PR interval (range 115–168 msec) was not significant (ρ = 0.107, P = 0.58).Reactivity to p200 is a dominant but not uniform anti–Ro 52 response in women whose children have CHB. Since exposure to this antibody specificity was observed with a similar frequency in children without CHB born to mothers with anti–Ro 52, additional factors are necessary to convert risk to disease expression. [ABSTRACT FROM AUTHOR]