Maternal antibody responses to the 52-kd SSA/RO p200 peptide and the development of fetal conduction defects
Robert M Clancy, Jill P Buyon, Keigo Ikeda, Kazuhisa Nozawa, Dionne A Argyle, Deborah M Friedman, Edward K L Chan, Robert M Clancy, Jill P Buyon, Keigo Ikeda, Kazuhisa Nozawa, Dionne A Argyle, Deborah M Friedman, Edward K L Chan
Abstract
Objective: To identify a finer level of antibody specificity for risk of congenital heart block (CHB) than reactivity to 52-kd SSA/Ro (Ro 52).
Methods: 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.
Results: 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 non-permeabilized 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 (rho = 0.107, P = 0.58).
Conclusion: 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.
Source: PubMed