Electrocardiographic abnormalities in a murine model injected with IgG from mothers of children with congenital heart block.
BACKGROUND
It is a widely held view that congenital heart block (CHB) is caused by the transplacental transfer of maternal autoantibodies (anti-SSA/Ro and/or anti-SSB/La) into the fetal circulation. To test this hypothesis and to reproduce human CHB, an experimental mouse model (BALB/c) was developed by passive transfer of human autoantibodies into pregnant mice.


RESULTS
Timed pregnant mice (n=54) were injected with a single intravenous bolus of purified IgG containing human anti-SSA/Ro and anti-SSB/La antibodies from mothers of children with CHB. To parallel the "window period" of susceptibility to CHB in humans, 3 groups of mice were used: 8, 11, and 16 days of gestation. Within each group, we tested 10, 25, 50, and 100 microg of IgG. At delivery, ECGs were recorded and analyzed for conduction abnormalities. Bradycardia and PR interval were significantly increased in 8-, 11-, and 16-day gestational groups when compared with controls (P<0.05). QRS duration was not significantly different between all groups. Antibody levels measured by ELISA in both mothers and their offspring confirmed the transplacental transfer of the human antibodies to the pups.


CONCLUSIONS
The passive transfer model demonstrated bradycardia, first-degree but not complete atrioventricular block in pups. The greater percentage and degree of bradycardia and PR prolongation in the 11-day mouse group correlates with the "window period" of susceptibility observed in humans. The high incidence of bradycardia suggests possible sinoatrial node involvement. All together, these data provide relevant insights into the pathogenesis of CHB.
Mazel
J A
JA
Cardiology Division, Veterans Administration Medical Center, and SUNY Health Science Center, Brooklyn, NY, USA.
El-Sherif
N
N
Buyon
J
J
Boutjdir
M
M
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology / Q000502:physiology*; D000974:Antibodies, Antinuclear / Q000032:analysis / Q000502:physiology; D001919:Bradycardia / Q000209:etiology / Q000503:physiopathology; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006327:Heart Block / Q000097:blood* / Q000151:congenital* / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D009035:Mothers; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; C035356:SS-A antibodies; C035357:SS-B antibodies