Specificity and effector mechanisms of autoantibodies in congenital heart block

Curr Opin Immunol. 2006 Dec;18(6):690-6. doi: 10.1016/j.coi.2006.09.012. Epub 2006 Sep 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • Female
  • Fetal Diseases / immunology*
  • Fetal Therapies
  • Heart Block / congenital*
  • Heart Block / immunology*
  • Heart Block / prevention & control
  • Humans
  • Myocytes, Cardiac / immunology
  • Myocytes, Cardiac / pathology
  • Pregnancy
  • Steroids, Fluorinated / therapeutic use

Substances

  • Autoantibodies
  • Autoantigens
  • Steroids, Fluorinated