© 1997 American Heart Association, Inc.
Articles |
Arrhythmogenicity of IgG and Anti–52-kD SSA/Ro Affinity-Purified Antibodies From Mothers of Children With Congenital Heart Block
the Division of Cardiology (M.B., L.C., Z.-H.Z., N.E.-S.), Veterans Administration Medical Center and State University of New York, Health Science Center, Brooklyn; the Department of Medicine (C.T., F.D., J.P.B.), Division of Rheumatology, New York University, and the Department of Rheumatic Diseases and Molecular Medicine (C.T., F.D., J.P.B.), Hospital for Joint Diseases, New York; and the Department of Obstetrics and Gynecology (W.R., A.M.), Beth Israel Medical Center, New York, NY.
Correspondence to Dr Mohamed Boutjdir, Cardiology Division (IIIA), VA Medical Center, 800 Poly Place, Brooklyn, NY 11209. E-mail boutjdir.mohamed@brooklyn.va.gov
An important advance in the description and understanding of congenital heart block (CHB) came in the 1970s with the observation that mothers of affected infants frequently had autoimmune diseases and, in particular, that many maternal sera contained antibodies to SSA/Ro and SSB/La ribonucleoproteins. Although the molecular biology of the candidate antigens has been extensively defined, the arrhythmogenic and electrophysiological effects of their cognate antibodies on the human fetal heart are unknown. In the present study, we provide evidence that IgG-enriched fractions and anti–52-kD SSA/Ro antibodies affinity-purified from sera of mothers whose children have CHB induce complete atrioventricular (AV) block in the human fetal heart perfused by the Langendorff technique and inhibit L-type Ca2+ currents at the whole-cell and single-channel level. Immunization of female BALB/c mice with recombinant 52-kD SSA/Ro protein generated high-titer antibodies that crossed the placenta during pregnancy and were associated with varying degrees of AV conduction abnormalities, including complete AV block, in the pups. These findings strongly suggest that anti–52-kD SSA/Ro antibodies are causally related to the development of CHB.
Key Words: human fetal heart • patch-clamp technique • L-type Ca2+ current • atrioventricular block • immunization
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