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*
Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine, New York, NY 10003;
Cardiology Division, Veterans Affairs Medical Center, Brooklyn, NY 11209; and
Scripps Research Institute, La Jolla, CA 92037
To correlate the arrhythmogenic effects of maternal autoantibodies
with the genesis of congenital heart block, female BALB/c mice were
immunized with human recombinant 48-kDa SSB/La, 60-kDa SSA/Ro, 52-kDa
SSA/Ro (52
), and 52ß (amino acids 169–245 deleted) as well as
with murine recombinant 52-kDa SSA/Ro. Control animals received
ß-galactosidase or a polypeptide encoded by pET-28 alone. Following
primary immunization and two boosters, high titer responses to the
respective Ags were established by ELISA, immunoblotting, and
immunoprecipitation. Sera from mice immunized with either human 52
or 52ß immunoprecipitated murine 52Ro. mRNA and protein expression of
52Ro was demonstrated in the newborn murine heart. A spectrum of
atrioventricular nodal conduction abnormalities was identified by
electrocardiogram. First-degree block was detected in 7% of 27
pups born to mothers immunized with 48La, 20% of 54 pups born to
60Ro-immunized mothers, 6% of 56 pups born to 52-immunized mothers,
7% of 86 pups born to 52ß-immunized mothers, and 9% of 22 pups born
to mothers immunized with murine 52Ro. Advanced conduction
abnormalities were only identified in offspring of 52- or
52ß-immunized mice. In the 52 group, one pup had complete block
and another had second-degree block (Wenckebach type); in the 52ß
group, five pups had complete block. Maternal Abs to the primary
immunogens were detected in the pups. No control had any conduction
abnormalities. This Ab-specific animal model provides strong evidence
for a pathogenic role of anti-SSA/Ro-SSB/La Abs, particularly 52Ro,
in the development of congenital heart block. The range and frequency
of conduction defects suggest that additional factors promote disease
expression.
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