Autoantibodies from mothers of children with congenital heart block downregulate cardiac L-type Ca channels.
Congenital heart block (CHB) affects offspring of mothers with autoantibodies (positive IgG) to intracellular SSA/Ro and SSB/La ribonucleoproteins and is associated with high morbidity and mortality. Here, we show that maternal anti-Ro/La antibodies immunoreact with human fetal cardiomyocyte sarcolemma, recognize human L-type Ca channel alpha(1C)-protein and functionally inhibit expressed current in oocytes injected with alpha(1C) cRNA and Purkinje L-type Ca current. Furthermore, cardiac myocytes from pups born to SSA/Ro-immunized mice exhibited reduced L-type Ca current density. All together, the data establish that L-type calcium channel is a target for maternal antibodies and may provide a functional basis for the electrocardiographic abnormalities seen in infants with CHB.
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Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System and SUNY Health Science Center, Brooklyn, New York 11209, USA.
Xiao
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Chen
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L
Boutjdir
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D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D020746:Calcium Channels, L-Type / Q000276:immunology / Q000378:metabolism*; D003429:Cross Reactions; D015536:Down-Regulation; D004594:Electrophysiology; D005260:Female; D006327:Heart Block / Q000151:congenital* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007231:Infant, Newborn; D051379:Mice; D009035:Mothers; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011233:Precipitin Tests; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011690:Purkinje Fibers; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins / Q000276:immunology*; D012508:Sarcolemma / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D014982:Xenopus laevis; D000097585:SS-B Antigen; D000099207:SS-A Antigen
D001323:Autoantibodies; D001324:Autoantigens; D020746:Calcium Channels, L-Type; D007074:Immunoglobulin G; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen; C419385:L-type calcium channel alpha(1C); C116006:RO60 protein, human