52-kDa Ro/SSA epitopes preferentially recognized by antibodies from mothers of children with neonatal lupus and congenital heart block.
52-kDa Ro/SSA epitopes preferentially recognized by antibodies from mothers of children with neonatal lupus and congenital heart block.
复制标题
52 kDa RO/SSA表位优先是由新生儿狼疮和先天性心脏块的儿童的母亲的抗体识别。
DOI：
10.1186/ar1848
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发表时间：
2006
影响因子：
4.9
通讯作者：
Muller, Sylviane
中科院分区：
文献类型：
--
作者：
Fritsch, Christine;Hoebeke, Johan;Dali, Hayet;Ricchiuti, Vincent;Isenberg, David A;Meyer, Olivier;Muller, Sylviane
新生儿红斑狼疮是一种罕见的疾病所造成的经胎盘通过母亲的自身抗体。52-kDa Ro/SSA抗原（Ro 52）核糖核蛋白代表了一种抗原靶点，其与患有新生儿狼疮和心脏传导障碍（主要是先天性心脏传导阻滞）的母亲的自身免疫反应密切相关。本研究的目的是确定与新生儿狼疮和先天性心脏传导阻滞相关的推定Ro 52/60-kDa Ro/SSA抗原（Ro 60）表位。采用Ro 52、Ro 60和48-kDa La/SSB抗原蛋白以及Ro 52/Ro 60蛋白的45个合成肽（13-24个残基长），通过ELISA研究了系统性红斑狼疮和干燥综合征母亲血清和无症状母亲血清中IgG抗体的反应性（对66名受试者的192份样本进行了纵向研究）。每个母亲在怀孕前、怀孕期间和怀孕后采集1至19个样本。随机抽取43例疾病对照和正常人血清进行平行检测。虽然没有发现干燥综合征和无症状的母亲组I，谁至少有一个新生儿狼疮，和组II，谁只有健康的婴儿，显着差异狼疮母亲从两组之间观察。在前一组狼疮母亲中，观察到Ro 52肽107-122和277-292的抗体频率显著较高。在妊娠18至30周之间，即风险期，与Ro 52肽1-13、277-292和365-382反应的抗体水平明显升高。Ro 52肽365-382的抗体先前已显示与心脏5-HT 4肾上腺素能受体的残基165-185交叉反应，并且可能在病理学上重要。这些Ro 52抗体亚群的水平在妊娠结束时和分娩后下降。因此，针对Ro 52肽1-13、107-122、277-292和365-382的IgG抗体可能代表预测具有Ro 52抗体的妊娠狼疮女性的并发症的重要生物标志物。
Neonatal lupus erythematosus is a rare disorder caused by the transplacental passage of maternal autoantibodies. The 52-kDa Ro/SSA antigen (Ro52) ribonucleoprotein represents an antigenic target strongly associated with the autoimmune response in mothers whose children have neonatal lupus and cardiac conduction disturbances, mainly congenital heart block. The objective of this study was to identify putative Ro52/60-kDa Ro/SSA antigen (Ro60) epitopes associated with neonatal lupus and congenital heart block. The reactivity of IgG antibodies present in the sera from mothers with systemic lupus erythematosus and Sjögren's syndrome and in the sera from asymptomatic mothers (a longitudinal study of 192 samples from 66 subjects) was investigated by ELISA using Ro52, Ro60 and 48-kDa La/SSB antigen proteins, as well as 45 synthetic peptides, 13–24 residues long, of Ro52/Ro60 proteins. One to 19 samples collected before, during and after pregnancy were available for each mother. Forty-three disease controls selected randomly and normal sera were tested in parallel. Although no differences were found between Sjögren's syndrome and asymptomatic mothers of group I, who had at least one infant with neonatal lupus, and of group II, who had healthy babies only, significant differences were observed between lupus mothers from both groups. In the former group of lupus mothers, a significantly higher frequency of antibodies to Ro52 peptides 107–122 and 277–292 was observed. Between 18 and 30 weeks of gestation, the period of risk, there was clearly an elevated level of antibodies reacting with Ro52 peptides 1–13, 277–292 and 365–382. Antibodies to Ro52 peptide 365–382 have been shown previously to cross-react with residues 165–185 of the heart 5-HT4 serotoninergic receptor, and might be pathologically important. The level of these Ro52 antibody subsets decreased at the end of pregnancy and after delivery. IgG antibodies to Ro52 peptides 1–13, 107–122, 277–292 and 365–382 may therefore represent important biomarkers to predict a complication in pregnant lupus women with Ro52 antibodies.