Boutjdir M, Chen L, Zhang Z H, Tseng C E, DiDonato F, Rashbaum W, Morris A, el-Sherif N, Buyon J P
Division of Cardiology, Veterans Administration Medical Center, Brooklyn, NY 11209, USA.
Circ Res. 1997 Mar;80(3):354-62. doi: 10.1161/01.res.80.3.354.
An important advance in the description and understanding of congenital heart block (CHB) came in the 1970s with the observation that mothers of affected infants frequently had autoimmune diseases and, in particular, that many maternal sera contained antibodies to SSA/Ro and SSB/La ribonucleoproteins. Although the molecular biology of the candidate antigens has been extensively defined, the arrhythmogenic and electrophysiological effects of their cognate antibodies on the human fetal heart are unknown. In the present study, we provide evidence that IgG-enriched fractions and anti-52-kD SSA/Ro antibodies affinity-purified from sera of mothers whose children have CHB induce complete atrioventricular (AV) block in the human fetal heart perfused by the Langendorff technique and inhibit L-type Ca2+ currents at the whole-cell and single-channel level. Immunization of female BALB/c mice with recombinant 52-kD SSA/Ro protein generated high-titer antibodies that crossed the placenta during pregnancy and were associated with varying degrees of AV conduction abnormalities, including complete AV block, in the pups. These findings strongly suggest that anti-52-kD SSA/Ro antibodies are causally related to the development of CHB.
20世纪70年代，先天性心脏传导阻滞（CHB）的描述和理解取得了一项重要进展，当时观察到受影响婴儿的母亲经常患有自身免疫性疾病，特别是许多母体血清中含有抗SSA/Ro和SSB/La核糖核蛋白的抗体。尽管候选抗原的分子生物学已被广泛定义，但其同源抗体对人类胎儿心脏的致心律失常和电生理作用尚不清楚。在本研究中，我们提供证据表明，从患有CHB孩子的母亲血清中亲和纯化的富含IgG的组分和抗52-kD SSA/Ro抗体，在采用Langendorff技术灌注的人类胎儿心脏中可诱发完全性房室（AV）传导阻滞，并在全细胞和单通道水平抑制L型Ca2+电流。用重组52-kD SSA/Ro蛋白免疫雌性BALB/c小鼠可产生高滴度抗体，这些抗体在怀孕期间穿过胎盘，并与幼崽不同程度的AV传导异常有关，包括完全性AV传导阻滞。这些发现强烈表明，抗52-kD SSA/Ro抗体与CHB的发生有因果关系。
