De Carolis Sara, Garufi Cristina, Garufi Ester, De Carolis Maria Pia, Botta Angela, Tabacco Sara, Salvi Silvia
Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Department of Obstetrics, Gynaecology and Pediatrics, Rome, Italy.
Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari, UOC Reumatologia, Sapienza University of Rome, Rome, Italy.
Front Pediatr. 2020 Dec 22;8:607515. doi: 10.3389/fped.2020.607515. eCollection 2020.
Autoimmune Congenital Heart Block (CHB) is an immune-mediated disease due to transplacental passage of circulating anti-Ro/SSA and anti-La/SSB autoantibodies. It occurs in 2% of anti-Ro/SSA-exposed pregnancies, and recurrence rate is nine times higher in subsequent pregnancies. Aim of this review is to identify biomarkers of CHB and treatment strategies. The Ro-system is constituted by two polypeptides targeted by the anti-Ro52 and anti-Ro60 autoantibodies. The central portion of Ro52 (p200), more than the full amino-acid sequence of Ro-52, is recognized to be the fine specificity of anti-Ro associated to the highest risk of cardiac damage. If anti-p200 antibody should be tested, as biomarker of CHB, over standard commercial ELISAs is still debated. Recent studies indicate that type I-Interferon (IFN) can activate fibroblasts in fetal heart. In the mother the anti-Ro/La antibodies activate the type I IFN-signature, and maternal IFN-regulated genes correlate with a similar neonatal IFN-gene expression. Evaluation of maternal IFN-signature could be used as novel biomarker of CHB. The measurement of "mechanical" PR interval with weekly fetal echocardiogram (ECHO) from 16 to at least 24 weeks of gestation is strongly recommended for CHB prenatal diagnosis. However, ECHO screening presents some limitations due to difficult identification of first-degree block and possible occurrence of a complete block from a normal rhythm in few days. Maternal administration of Hydroxychloroquine from the tenth week of gestation, modulating toll-like receptor and autoantibody-dependent type I IFN activation on the fetus, has an important role in preventing CHB in pregnant women with high risk for recurrent CHB.
自身免疫性先天性心脏传导阻滞（CHB）是一种免疫介导的疾病，由循环中的抗Ro/SSA和抗La/SSB自身抗体经胎盘传递所致。它发生在2%暴露于抗Ro/SSA的妊娠中，后续妊娠的复发率高出九倍。本综述的目的是确定CHB的生物标志物和治疗策略。Ro系统由抗Ro52和抗Ro60自身抗体靶向的两种多肽组成。Ro52的中央部分（p200），而非Ro-52的完整氨基酸序列，被认为是与心脏损伤最高风险相关的抗Ro的精细特异性。作为CHB的生物标志物，是否应检测抗p200抗体，相较于标准商业酶联免疫吸附测定（ELISA）仍存在争议。最近的研究表明，I型干扰素（IFN）可激活胎儿心脏中的成纤维细胞。在母亲体内，抗Ro/La抗体激活I型IFN特征，母体IFN调节基因与类似的新生儿IFN基因表达相关。评估母体IFN特征可作为CHB的新型生物标志物。强烈建议从妊娠16周至少至24周每周进行胎儿超声心动图（ECHO）检查以测量“机械性”PR间期，用于CHB的产前诊断。然而，ECHO筛查存在一些局限性，因为难以识别一度房室传导阻滞，且在数天内可能从正常心律转变为完全性房室传导阻滞。从妊娠第10周起母体给予羟氯喹，调节胎儿的Toll样受体和自身抗体依赖性I型IFN激活，在预防复发性CHB高风险孕妇发生CHB方面具有重要作用。
