Eilat D
Département de Médecine A, Hôpital Universitaire Hadassah, Jérusalem, Israël.
Ann Med Interne (Paris). 1990;141(3):205-7.
A detailed analysis of variable region sequences, derived from monoclonal lupus anti-DNA autoantibodies has led to several conclusions with respect to the etiology and pathogenesis of systemic lupus erythematosus (SLE). It was found that the gene elements which are expressed in anti-DNA heavy and light chains are present in the germ lines of normal and diseased animals. However, several VH gene segments are not normally expressed in antibodies to external antigens and may, therefore, be excluded by the regulatory mechanism of self-tolerance. The presence of somatic point mutations, which may serve to change antigenic specificity as well as to increase affinity, indicates that an antigen (DNA)-driven mechanism rather than a polyclonal activation is responsible for the autoimmune response in SLE. An additional unique motif of anti-DNA heavy chains was found to consist of an arginine-rich basic peptide in the third complementarity-determining (hypervariable) region. These data have enabled us to build a computer model of the anti-DNA binding site and to design specific inhibitors of the autoimmune reaction.
对源自单克隆狼疮抗DNA自身抗体的可变区序列进行的详细分析，就系统性红斑狼疮（SLE）的病因和发病机制得出了几个结论。研究发现，在抗DNA重链和轻链中表达的基因元件存在于正常和患病动物的种系中。然而，几个VH基因片段在针对外部抗原的抗体中通常不表达，因此可能被自身耐受的调节机制排除。体细胞点突变的存在可能会改变抗原特异性并增加亲和力，这表明抗原（DNA）驱动机制而非多克隆激活是SLE自身免疫反应的原因。发现抗DNA重链的另一个独特基序由位于第三个互补决定（高变）区的富含精氨酸的碱性肽组成。这些数据使我们能够构建抗DNA结合位点的计算机模型，并设计自身免疫反应的特异性抑制剂。
