活化染色质诱导SLE样综合征的启动原研究

ystemic Lupus Erythematosis(SLE) is a severe autoimmune disease, characterized by production of various antinuclear antibodies(ANA).Until now the etiology of SLE remains elusive, because it has not been elucidated what initiator induces the production of ANAs. Once we immunized nonautoimmune predisposed BALB/c mice with activated lymphocytes and their chromatin, all kinds of ANAs were produced. In order to find out what component of the chromatin from activated lymphocytes induces the production of ANA, we extracted DNA and histone from active chromatin and constructed the expression plasmid based on the major epitope of Sm autoantigen, then immunized syngeneic Balb/c mice respectively. We found that all the immunization mentioned above could induce the production of anti-DNA, anti-histone autoantibodies and deposition of immune complex in glomerulus. We observed fatherly that DNA was demethylated when lymphocytes were activated, while this did not alter its immunogenicity. Serine was obviously phosphorylated in the H1 component of active histone, dephosphorylation could affect the titers of antinuclear antibodies, which suggested that serine phosphorylation plays certain role in the immunogenicity of histone. Gene immunization based on the Sm epitope could cause epitope spreading. We put forth that the components of activated lymphocytes are the real initiators of ANA production, lymphocytes activation is the common pathway of the etiology of SLE, which would have deep influence on the theoretic research and treatment strategy of this disease.

目的：寻找活化淋巴细胞核染色质诱导SLE的启动原；方法：从活化淋巴细胞核中分离染色剩崛』钚訢NA和组蛋白以及构建SM抗原主要表位基因质粒,分别免疫同系动物，动态观察笵NA,抗SM,抗组蛋白等抗核抗体(ANA)及SLE样综合征；预期上述各组均可诱导ANA和SLE样综合征产生；从而证明活性淋巴细胞有抗原质和量变化，是启动ANA生成的启动原。