LFA-1（CD11a）甲基化状态与多发性硬化发病机制研究
发布时间：2018-12-13 03:14
【摘要】：目的探讨多发性硬化患者外周血CD4T淋巴细胞LFA-1启动子序列甲基化状态是否存在异常；同时探究甲基化状态的异常是否与患者病情严重程度及预后因素相关，明确甲基化状态的改变能否作为病情诊断及预后判断的指标。方法选择临床诊断明确、处于发病急性期且未接受免疫抑制或免疫调节治疗的缓解复发型多发性硬化患者21名，留取其血液标本，，记录其发病全过程及本次发病时扩展的残疾状况量表(expanded disability status scale,EDSS)评分，并行腰椎穿刺及头颅MRI增强扫描检查；21名患者中有11名曾于缓解期于我院住院复查，再次留取外周血标本，共计32例血液标本纳入实验组。选择与患者年龄、性别相匹配的健康者32名，同样留取外周血标本纳入对照组。检测血标本中CD4T淋巴细胞CD11a表达基因启动子序列甲基化状态，并进行对照分析。结果在整体的血标本检测中，多发性硬化患者CD4T淋巴细胞CD11a表达基因启动子序列甲基化状态与正常对照相比，二者间并不存在显统计学差异（p＞0.05）；但对于处发病急性期患者的那部分血标本其甲基化状态要低于正常对照组（p＜0.05）；同时对于同一患者，处发病急性期时其甲基化状态要较处缓解期时低（p＜0.05）；但患者DNA甲基化状态与首发症状是否有括约肌功能障碍、首次发作与第二次发作时间间隔长短、脑脊液寡克隆带是否阳性、头颅MRI是否出现出现环形强化、EDSS评分的高低及患病病程长短等临床特征并不存在相关性（p＞0.05）。结论CD4T淋巴细胞CD11a表达基因启动子序列甲基化状态至少与多发性硬化的发病状态相关，且这种甲基化状态的改变与标本的冷冻保存无关；但甲基化状态的差异并不能反映发病时的病情严重程度或作为判断预后的指标；同时目前仍不能明确这种甲基化状态的改变与多发性硬化发病存在何种关联。
[Abstract]:Objective to investigate whether there is abnormal methylation of LFA-1 promoter sequence in peripheral CD4T lymphocytes of patients with multiple sclerosis. At the same time, to explore whether the abnormal methylation status is related to the severity of the patient's condition and prognostic factors, and to determine whether the change of the methylation state can be used as an indicator of the diagnosis and prognosis of the disease. Methods A total of 21 patients with relapsed multiple sclerosis (MS) with definite clinical diagnosis and no immunosuppressive or immunomodulatory therapy were selected and their blood samples were collected. The (expanded disability status scale,EDSS scores of the whole course of the disease and the extended disability status scale were recorded, and the lumbar puncture and cranial MRI enhanced scanning were performed. Of the 21 patients, 11 had been reexamined in our hospital during remission period, and 32 blood samples were collected from the experimental group. Thirty-two healthy subjects matched with age and sex were enrolled in the control group. The methylation status of promoter sequence of CD11a expression gene in CD4T lymphocytes was detected and compared. Results in the whole blood samples, there was no significant difference between the methylation status of the promoter sequence of CD11a expression gene in CD4T lymphocytes of patients with multiple sclerosis and that of normal controls (p > 0. 05). However, the methylation status of the blood samples of the patients in the acute stage of the disease was lower than that of the normal control group (p < 0.05). At the same time, the methylation status of the patients in the acute stage was lower than that in the remission stage (p < 0.05). However, whether there were sphincter dysfunction, the interval between the first episode and the second episode, the positive oligoclonal bands in cerebrospinal fluid, and the circular enhancement of cranial MRI were found in the patients with DNA methylation and initial symptoms. There was no correlation between the EDSS score and the duration of the disease (p > 0. 05). Conclusion the methylation status of the promoter sequence of CD11a expression gene in CD4T lymphocytes is at least related to the pathogenesis of multiple sclerosis, and the change of this methylation state is not related to the cryopreservation of the specimens. However, the difference of methylation status can not reflect the severity of the disease at the time of onset or as a prognostic indicator, and it is still not clear how the change of methylation status is associated with the pathogenesis of multiple sclerosis.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R744.51
本文编号：2375769
[Abstract]:Objective to investigate whether there is abnormal methylation of LFA-1 promoter sequence in peripheral CD4T lymphocytes of patients with multiple sclerosis. At the same time, to explore whether the abnormal methylation status is related to the severity of the patient's condition and prognostic factors, and to determine whether the change of the methylation state can be used as an indicator of the diagnosis and prognosis of the disease. Methods A total of 21 patients with relapsed multiple sclerosis (MS) with definite clinical diagnosis and no immunosuppressive or immunomodulatory therapy were selected and their blood samples were collected. The (expanded disability status scale,EDSS scores of the whole course of the disease and the extended disability status scale were recorded, and the lumbar puncture and cranial MRI enhanced scanning were performed. Of the 21 patients, 11 had been reexamined in our hospital during remission period, and 32 blood samples were collected from the experimental group. Thirty-two healthy subjects matched with age and sex were enrolled in the control group. The methylation status of promoter sequence of CD11a expression gene in CD4T lymphocytes was detected and compared. Results in the whole blood samples, there was no significant difference between the methylation status of the promoter sequence of CD11a expression gene in CD4T lymphocytes of patients with multiple sclerosis and that of normal controls (p > 0. 05). However, the methylation status of the blood samples of the patients in the acute stage of the disease was lower than that of the normal control group (p < 0.05). At the same time, the methylation status of the patients in the acute stage was lower than that in the remission stage (p < 0.05). However, whether there were sphincter dysfunction, the interval between the first episode and the second episode, the positive oligoclonal bands in cerebrospinal fluid, and the circular enhancement of cranial MRI were found in the patients with DNA methylation and initial symptoms. There was no correlation between the EDSS score and the duration of the disease (p > 0. 05). Conclusion the methylation status of the promoter sequence of CD11a expression gene in CD4T lymphocytes is at least related to the pathogenesis of multiple sclerosis, and the change of this methylation state is not related to the cryopreservation of the specimens. However, the difference of methylation status can not reflect the severity of the disease at the time of onset or as a prognostic indicator, and it is still not clear how the change of methylation status is associated with the pathogenesis of multiple sclerosis.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R744.51
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