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自身免疫性风湿疾病患者血液、滑膜单核细胞及滑膜组织中DNA的5-甲基胞嘧啶含量

5-Methylcytosine content of DNA in blood, synovial mononuclear cells and synovial tissue from patients affected by autoimmune rheumatic diseases.

作者信息

Corvetta A, Della Bitta R, Luchetti M M, Pomponio G

机构信息

Istituto di Clinica Medica Generale e Terapia Medica dell' Università di Ancona, Ospedale Generale Regionale, Italy.

出版信息

J Chromatogr. 1991 May 31;566(2):481-91. doi: 10.1016/0378-4347(91)80265-e.

DOI:10.1016/0378-4347(91)80265-e
PMID:1939459
Abstract

The percentage of 5-methylcytosine (m5Cyt) has been determined in peripheral blood, synovial mononuclear cells and synovial tissue from patients affected by various rheumatic autoimmune diseases. The determination was performed by reversed-phase high-performance liquid chromatography. Fifteen controls were compared to twenty-one patients affected by rheumatoid arthritis and to nine patients affected by systemic lupus erythematosus. The mean percentage of m5Cyt in normal individuals was significantly higher than in the rheumatoid arthritis and systemic lupus erythematosus patients. In addition, patients with active disease showed lower values than patients in remission. This finding is in agreement with the hypothesis that DNA hypomethylation may play a role in the pathogenesis of the autoimmune diseases, resulting in altered oncogene expression. Therapy with cyclosporin A led to a decrease in the percentage of m5Cyt in three rheumatoid arthritis patients, but a rebound was observed when the cyclosporin A was suspended. The percentage of m5Cyt in the DNA of synovial tissue from four rheumatoid arthritis patients and five patients with osteoarthritis was similar; this observation confirms that, in addition to disease-specific and disease activity-specific variations, the percentage of m5Cyt may also show tissue-specific variations.

摘要

已测定了各类风湿性自身免疫疾病患者外周血、滑膜单核细胞及滑膜组织中5-甲基胞嘧啶(m5Cyt)的百分比。测定采用反相高效液相色谱法进行。将15名对照者与21名类风湿关节炎患者及9名系统性红斑狼疮患者进行了比较。正常个体中m5Cyt的平均百分比显著高于类风湿关节炎患者和系统性红斑狼疮患者。此外,处于疾病活动期的患者的值低于缓解期患者。这一发现与DNA低甲基化可能在自身免疫疾病发病机制中起作用并导致癌基因表达改变的假说一致。环孢素A治疗使3名类风湿关节炎患者的m5Cyt百分比降低,但停用环孢素A后出现了反弹。4名类风湿关节炎患者和5名骨关节炎患者滑膜组织DNA中的m5Cyt百分比相似;这一观察结果证实,除了疾病特异性和疾病活动特异性变化外,m5Cyt百分比也可能表现出组织特异性变化。

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