Unit of Experimental Rheumatology, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
Department of Women and Child Health, Karolinska Institutet, 171 76 Stockholm, Sweden.
Exp Cell Res. 2014 Jul 1;325(1):2-9. doi: 10.1016/j.yexcr.2014.01.003. Epub 2014 Jan 13.
Autoantibody-associated congenital heart block (CHB) is a passively acquired autoimmune condition associated with maternal anti-Ro/SSA antibodies and primarily affecting electric signal conduction at the atrioventricular node in the fetal heart. CHB occurs in 1-2% of anti-Ro/SSA antibody-positive pregancies and has a recurrence rate of 12-20% in a subsequent pregnancy. Despite the long-recognized association between maternal anti-Ro/SSA autoantibodies and CHB, the molecular mechanisms underlying CHB pathogenesis are not fully understood, but several targets for the maternal autoantibodies in the fetal heart have been suggested. Recent studies also indicate that fetal susceptibility genes determine whether an autoantibody-exposed fetus will develop CHB or not, and begin to identify such genes. In this article, we review the different lines of investigation undertaken to elucidate the molecular pathways involved in CHB development and reflect on the hypotheses put forward to explain CHB pathogenesis as well as on the questions left unanswered and that should guide future studies.
自身抗体相关性先天性心脏传导阻滞（CHB）是一种被动获得性自身免疫性疾病，与母体抗 Ro/SSA 抗体相关，主要影响胎儿心脏房室结的电信号传导。CHB 发生在 1-2%的抗 Ro/SSA 抗体阳性妊娠中，在随后的妊娠中复发率为 12-20%。尽管母体抗 Ro/SSA 自身抗体与 CHB 之间的关联早已被认识，但 CHB 发病机制的分子机制尚不完全清楚，但已经提出了母体自身抗体在胎儿心脏中的几个靶标。最近的研究还表明，胎儿易感基因决定了一个暴露于自身抗体的胎儿是否会发展为 CHB，并开始鉴定此类基因。在本文中，我们回顾了为阐明 CHB 发展中涉及的分子途径而进行的不同研究，并反思了为解释 CHB 发病机制而提出的假说，以及未解决的问题，这些问题应指导未来的研究。
