Arrhythmogenicity of IgG and anti-52-kD SSA/Ro affinity-purified antibodies from mothers of children with congenital heart block
Arrhythmogenicity of IgG and anti-52-kD SSA/Ro affinity-purified antibodies from mothers of children with congenital heart block
复制标题
DOI：
10.1161/01.res.80.3.354
复制
发表时间：
1997-03-01
影响因子：
20.1
通讯作者：
Buyon, JP
中科院分区：
文献类型：
--
作者：
Boutjdir, M;Chen, L;Buyon, JP
20世纪70年代，对先天性心脏传导阻滞（CHB）的描述和理解取得了重要进展，观察到受影响婴儿的母亲经常患有自身免疫性疾病，特别是许多母亲血清含有SSA/Ro和SSB/La核糖核蛋白的抗体。虽然候选抗原的分子生物学已被广泛定义，但其同源抗体对人胎心的致瘤性和电生理学作用尚不清楚。在本研究中，我们提供的证据表明，IgG富集馏分和抗52-kD SSA/Ro抗体亲和纯化的母亲的血清中的儿童有CHB诱导完全房室（AV）阻滞在人胎心灌注Langendorff技术和抑制L型钙电流在全细胞和单通道水平。用重组52 kD SSA/Ro蛋白免疫雌性BALB/c小鼠产生高滴度抗体，这些抗体在妊娠期间穿过胎盘，并与幼崽中不同程度的AV传导异常（包括完全AV阻滞）相关。这些发现强烈提示抗52-kD SSA/Ro抗体与CHB的发展有因果关系。
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.