Specificity and effector mechanisms of autoantibodies in congenital heart block.
Complete congenital atrio-ventricular (AV) heart block develops in 2-5% of fetuses of Ro/SSA and La/SSB autoantibody-positive pregnant women. During pregnancy, the Ro/SSA and La/SSB antibodies are transported across the placenta and affect the fetus. Emerging data suggest that this happens by a two-stage process. In the first step, maternal autoantibodies bind fetal cardiomyocytes, dysregulate calcium homestasis and induce apoptosis in affected cells. This step might clinically correspond to a first-degree heart block, and be reversible. La/SSB antibodies can bind apoptotic cardiomyocytes and thus increase Ig deposition in the heart. The tissue damage could, as a second step, lead to spread of inflammation in genetically pre-disposed fetuses, progressing to fibrosis and calcification of the AV-node and subsequent complete congenital heart block. Early intrauterine treatment of an incomplete AV-block with fluorinated steroids has been shown to prevent progression of the heart block, making it clinically important to find specific markers to identify the high-risk pregnancies.
Wahren-Herlenius
Marie
M
Rheumatology Unit, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden. marie.wahren@ki.se
Sonesson
Sven-Erik
SE
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D005260:Female; D005315:Fetal Diseases / Q000276:immunology*; D046128:Fetal Therapies; D006327:Heart Block / Q000151:congenital* / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D032383:Myocytes, Cardiac / Q000276:immunology / Q000473:pathology; D011247:Pregnancy; D013259:Steroids, Fluorinated / Q000627:therapeutic use
D001323:Autoantibodies; D001324:Autoantigens; D013259:Steroids, Fluorinated