系统性红斑狼疮外周血单个核细胞羟甲基化水平与临床表型的相关性研究

发布时间：2018-05-30 22:23

本文选题：系统性红斑狼疮 + 5-羟甲基化胞嘧啶　；参考：《昆明医科大学》2017年硕士论文

【摘要】：[目的]通过检测系统性红斑狼疮(systemiclupuserythematosus,SLE)患者和正常对照外周血单个核细胞DNA羟甲基化的水平,分析DNA羟甲基化与SLE的关系;同时探索SLE患者的羟甲基化与合并症及临床表型之间的关系。[方法]本研究首次采用ELISA法检测95例SLE患者及77例正常健康对照者外周单个核细胞DNA5-羟甲基胞嘧啶(5-hydroxymethylcytosine,5-hmC)的水平,比较两者之间的差异,分析DNA羟甲基化水平与SLE的关系。同时收集患者相关实验室检查,对SLE患者5-hmC的水平与系统性红斑狼疮患者合并症及临床表型之间的相关性进行统计、比较,从而了解5-hmC含量的改变与系统性红斑狼疮相关的合并症及临床表型的关系。[结果](1)本研究共纳入SLE患者95例,其中男性17例,女性78例,年龄在16-60岁,平均年龄35.38± 14.39岁;对照组为77例,其中男性为16例,女性61例,年龄在16-60岁,平均年龄在37.22 士 13.92岁。患者组和正常对照组之间性别、年龄均无明显统计学差异(P0.05)。(2)SLE 患者 5-hmC 平均含量为 0.063±0.0029%,对照组为 0.069±0.0032%,SLE患者羟甲基水平下降约0.006%,差异有显著统计学差异(t=12.468,P0.001)。进一步分析发现,SLE患者5-hmC的含量与SLEDAI评分呈负相关关系(r=-0.317,P =0.004)。(3)SLE患者的5-hmC水平分别与总胆红素(r=0.223,P=0.033)、直接胆红素(r=0.213,P=0.043)、间接胆红素(r=0.247,P=0.018)及 k 链(r=0.399,P=0.011)正相关,进一步分析发现,SLEDAI评分分别与总胆红素(r =-0.311,P=0.005)、直接胆红素(r=-0.244,P=0.030)、间接胆红素(r =-0.290,P=0.009)呈负相关;SLE患者的5-hmC水平分别与尿微量白蛋白(r=-0.330,P =0.007)及尿白蛋白肌酐比值(r=-0.265,P=0.031)负相关。但相关系数r绝对值在0.2-0.4之间,相关性为低度相关,结果有待进一步扩大样本验证。(4)无肾炎SLE患者5-hmC含量高于SLE合并肾炎(SLE+LN)患者5-hmC含量(0.062 vs0.064,P=0.027);SLE患者5-hmC含量高于SLE+高血压患者5-hmC含量(0.062vs0.064,P=0.021);而SLE继发干燥综合征、抗磷脂综合征、NPSLE、血液系统受累、甲状腺疾病、感染等合并症时,5-hmC含量变化不明显(P0.05)。(5)核小体抗体阴性SLE患者5-hmC含量高于核小体抗体阳性患者(P=0.043),差异有统计学意义,而与所检测的ANA滴度、ANA核型、ds-DNA抗体、抗组蛋白抗体、Sm抗体、U1snRNP抗体、SSA-RO60KD抗体、SSA-R052KD抗体、SSB抗体、抗核糖体抗体之间不存在统计学差异。[结论](1)SLE外周血DNA5-hmC可能存在改变,可能参与了 SLE的发病。(2)SLE患者外周血5-hmC的含量与SLE疾病严重程度呈负相关,或可作为SLE活动度的标志物。(3)5-hmC含量降低与狼疮性肾炎的发生相关,因此检测5-hmC含量或可有利于早期发现狼疮性肾炎。(4)5-hmC可能影响某些自身抗体的产生(尤其是核小体抗体),参与自身免疫过程。
[Abstract]:[objective] to analyze the relationship between DNA hydroxymethylation and SLE in peripheral blood mononuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE) and normal controls. At the same time, to explore the relationship between hydroxymethylation and complications and clinical phenotypes in patients with SLE. [methods] the peripheral mononuclear cells DNA5-hydroxymethylcytosine 5-HmC- (5-HMC) levels in 95 patients with SLE and 77 healthy controls were detected by ELISA method for the first time, and the relationship between DNA hydroxymethylation and SLE was analyzed. At the same time, the correlation between the 5-hmC level of SLE patients and the complications and clinical phenotypes of patients with systemic lupus erythematosus was analyzed and compared. To understand the relationship between the changes of 5-hmC content and systemic lupus erythematosus associated complications and clinical phenotypes. [results] A total of 95 patients with SLE were included in this study, including 17 males and 78 females, with an average age of 35.38 卤14.39 years, and 77 patients in the control group (16 males and 61 females, aged 16-60 years). The average age was 37.22 卤13.92 years old. There was no significant difference in sex and age between the patient group and the normal control group. The average content of 5-hmC in the patients with SLE was 0.063 卤0.0029, while that in the control group was 0.069 卤0.0032. The level of hydroxymethyl decreased by 0.006. There was a significant difference between the two groups. Further analysis showed that there was a negative correlation between the 5-hmC content and the SLEDAI score. The 5-hmC levels were positively correlated with the total bilirubin level 0.223P 0.033, direct bilirubin 0.213P 0.43, indirect bilirubin 0.247P0. 018) and k chain ru 0.399P0. 011), respectively. Further analysis showed that the SLEDAI score was negatively correlated with the total bilirubin r-0.311P0. 005, direct bilirubin r-0.244 P0. 030, indirect bilirubin r-0.290 P0. 009), and the 5-hmC level negatively correlated with the urinary albumin r-0. 330 P0. 007) and the urinary albumin creatinine ratio (r-0. 265 P 0. 031). But the absolute value of correlation coefficient r is between 0.2-0.4, the correlation is low correlation, Results the content of 5-hmC in SLE patients without glomerulonephritis was higher than that in patients with SLE combined with glomerulonephritis. The content of 5-hmC in patients with SLE hypertension was higher than that in patients with SLE hypertension, while that in patients with SLE secondary to Sjogren's syndrome was higher than that in patients with SLE hypertension. In patients with antiphospholipid syndrome, blood system involvement, thyroid disease, infection and other complications, the level of 5-hmC in patients with negative nucleosome antibody was higher than that in patients with positive nucleosome antibody (P 0.043), and there was no significant change in the content of 5-HMC in patients with complicated diseases such as thyroid disease and infection. However, there was no statistical difference between the ANA titer and the detected ANA karyotypes, such as anti-histone antibody, U1snRNP antibody, SSA-RO60KD antibody, SSA-R052KD antibody, and anti-ribosomal antibody. [conclusion] there may be changes in peripheral blood DNA5-hmC in patients with SLE, which may be involved in the negative correlation between the 5-hmC content in peripheral blood and the severity of SLE disease, or as a marker of SLE activity. The decrease of 5-HMC level may be associated with the occurrence of lupus nephritis. Therefore, the detection of 5-hmC may be helpful to the early detection of lupus nephritis. 45-HMC may affect the production of some autoantibodies (especially nucleosome antibody), and participate in the autoimmune process.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.241

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