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首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Analysis of a sequenced cDNA library from multiple sclerosis lesions.
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Analysis of a sequenced cDNA library from multiple sclerosis lesions.

机译：分析来自多发性硬化病病变的测序cDNA文库。

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摘要

To identify genes that are expressed in MS pathogenesis, we have analyzed a normalized cDNA library made from mRNA obtained from CNS lesions of a patient with primary progressive MS. Complementary DNA clones obtained from this library were subjected to automated DNA sequencing to generate expressed sequence tags. Analysis of this MS cDNA library revealed the presence of 54 cDNAs that were associated with immune activation and indicated the presence of an ongoing inflammatory response with evidence of both cell-mediated and humoral immune responses. The surprising finding was that 16 of the cDNAs encoded autoantigens associated with seven other autoimmune disorders, while only three of these 16 autoantigen cDNAs were present in a similarly constructed adult brain library. Such aberrant autoantigen expression could provide a source of secondary autoimmune stimulation that could contribute to the ongoing inflammatory response in MS. In addition, two cDNAs were found that mapped to a known MS susceptibility locus (5p14-p12): one encoded an excitatory amino acid transporter and the other a human homologue of the Drosophila disabled gene. This approach to the molecular biology of MS pathogenesis may help to illuminate previously unappreciated aspects of this disease.
机译：为了鉴定在MS发病机制中表达的基因，我们分析了一个标准化的cDNA文库，该文库由从患有原发性进行性MS的患者的CNS病变获得的mRNA制成。将从该文库获得的互补DNA克隆进行自动DNA测序，以生成表达的序列标签。对该MS cDNA文库的分析揭示了与免疫激活相关的54个cDNA的存在，并表明正在进行的炎性反应的存在，同时具有细胞介导的和体液免疫反应的证据。令人惊讶的发现是，其中16个cDNA编码与其他7种自身免疫性疾病相关的自身抗原，而这16个自身抗原cDNA中只有3个存在于类似构建的成人脑文库中。这种异常的自身抗原表达可以提供二次自身免疫刺激的来源，其可以促进MS中持续的炎症反应。此外，还发现了两个定位到已知MS易感基因座（5p14-p12）的cDNA：一个编码兴奋性氨基酸转运蛋白，另一个编码果蝇禁用基因的人类同源物。 MS发病机理的分子生物学方法可能有助于阐明该疾病以前未被认识的方面。

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