Tsuzaka K, Takeuchi T, Onoda N, Pang M, Abe T
Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, 1981 Kamoda, Kawagoe, Saitama 350, Japan.
J Autoimmun. 1998 Oct;11(5):381-5. doi: 10.1006/jaut.1998.0223.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown aetiology. Although it has been reported that T cells might be responsible for the pathogenesis of SLE, it remains unclear whether immune aberrations of SLE T cells are the primary event in this pathological process. We have recently reported that tyrosine phosphorylation and expression of the T cell receptor zeta chain (TCR zeta) was significantly decreased in SLE T cells and that two SLE patients exhibited a 36 bp, exon 7 deletion of the TCR zeta mRNA. To investigate further common mutations in TCR zeta mRNA among SLE patients, mRNA was isolated from the peripheral blood T cells of two normal controls, two systemic sclerosis (SSc) patients, and eight SLE patients. TCR zeta cDNA was amplified by RT-PCR. Five out of the eight SLE patients exhibited abnormal migration patterns of the TCR zeta cDNA in PCR single stranded conformational polymorphism analysis. PCR products were ligated into pUC18 and five clones obtained were sequenced. Analysis of the nucleotide sequences revealed that all of the five pUC18 clones from the normal controls and SSc patients had the normal nucleotide sequence, whereas all eight SLE patients had mutations in TCR zeta cDNA accompanied by predicted amino acid substitutions. Mutations found in six of these patients corresponded to those of the third immunoreceptor tyrosine-based activation motif (ITAM) domain or the GTP/GDP binding site in TCR zetaThus, these mutations in TCR zeta mRNA could be responsible for the decreased expression of the TCR zeta protein in SLE T cells.
系统性红斑狼疮（SLE）是一种病因不明的全身性自身免疫性疾病。尽管有报道称T细胞可能与SLE的发病机制有关，但SLE T细胞的免疫异常是否是这一病理过程中的主要事件仍不清楚。我们最近报道，SLE T细胞中酪氨酸磷酸化和T细胞受体ζ链（TCRζ）的表达显著降低，并且两名SLE患者的TCRζ mRNA存在36bp的外显子7缺失。为了进一步研究SLE患者中TCRζ mRNA的常见突变，从两名正常对照、两名系统性硬化症（SSc）患者和八名SLE患者的外周血T细胞中分离mRNA。通过RT-PCR扩增TCRζ cDNA。在PCR单链构象多态性分析中，八名SLE患者中有五名表现出TCRζ cDNA的异常迁移模式。将PCR产物连接到pUC18中，并对获得的五个克隆进行测序。核苷酸序列分析显示，来自正常对照和SSc患者的所有五个pUC18克隆具有正常的核苷酸序列，而所有八名SLE患者的TCRζ cDNA均有突变，并伴有预测的氨基酸替换。在其中六名患者中发现的突变与TCRζ中第三个基于免疫受体酪氨酸的激活基序（ITAM）结构域或GTP/GDP结合位点的突变相对应。因此，TCRζ mRNA中的这些突变可能是SLE T细胞中TCRζ蛋白表达降低的原因。
