细胞因子检测在抗N-甲基-D-天冬氨酸受体脑炎诊治中的应用价值研究

发布时间：2018-03-10 05:03

本文选题：抗N-甲基-D-天冬氨酸受体脑炎　切入点：细胞因子　出处：《北京协和医学院》2016年博士论文　论文类型：学位论文

【摘要】：研究目的：抗N-甲基-D-天冬氨酸受体脑炎(抗NMDAR脑炎)是最常见的一类自身免疫性脑炎。其临床表现复杂多样,多起病急骤、进展较快,病情严重程度复杂不一。近年来对于抗NMDAR脑炎的发病机制研究,提示体内产生特异性的抗GluN1抗体是致病的直接原因；但抗体上游的免疫机制尚不清楚。目前临床上诊断依赖脑脊液特异性的抗GluN1抗体阳性。临床病情评估方式主要包括临床症状、改良Rankin评分、脑脊液抗体滴度和鞘内IgG合成率等。我们检测了抗NMDAR脑炎患者脑脊液与血清的细胞因子水平,分析其对抗NMDAR脑炎的临床意义。研究方法：收集52例明确抗NMDAR脑炎、13例炎性对照组、6例非炎性对照组患者的脑脊液与血清标本,用酶联免疫分析(ELISA)法检测其中CXCL13、BAFF、 APRIL、IL-6和CXCL10等5种细胞因子水平。使用SPSS IBM 20.0软件对实验数据进行统计分析,对比不同疾病组间、急性期与缓解期细胞因子的均值差异,及影响急性期脑脊液细胞因子水平的可能因素。研究结果：(1)血清APRIL在实验组与非炎性对照组之间的分布存在显著差异(Sidak事后检验：P=0.004)。脑脊液细胞因子水平对照组比较具有升高趋势,未见统计学差异,可能与对照组例数不足有关。(2) CXCL13、BAFF和IL-6在急性期与缓解期患者脑脊液之间的分布存在显著差异(分别P=0.050；P=0.014；P=0.041)；BAFF在急性期与缓解期患者血清之间的分布存在显著差异(P=0.022)。(3)患者年龄与脑脊液CXCL13水平相关；脑脊液淋巴细胞炎症影响IL-6水平；脑脊液CXCL10与患者年龄、mRS相关,治疗与否亦影响水平；脑脊液BAFF、APRIL水平与患者临床特征不相关。(4)2例周期性鞘注病例的脑脊液BAFF、IL-6、CXCL10的水平,与脑脊液抗GluN1抗体滴度的变化趋势基本符合；急性期(免疫治疗)后脑脊液CXCL13迅速回落到正常水平。结论：以B细胞为核心、Th17辅助的鞘内体液免疫反应可能是抗NMDAR脑炎主要的免疫机制；除鞘内的免疫反应外,还存在全身体液免疫激活。抗NMDAR脑炎患者的脑脊液CXCL13、BAFF、IL-6,以及血清BAFF是病情评价和观察治疗反应潜在的生物标志物。脑脊液淋巴细胞炎症与脑脊液IL-6水平相关,年龄可能影响CXCL13的水平。多种细胞因子与抗体滴度的变化趋势相一致。
[Abstract]:Objective: Anti-N- methyl-Daspartic acid receptor encephalitis (NMDAR encephalitis) is the most common type of autoimmune encephalitis. Recent studies on the pathogenesis of anti NMDAR encephalitis suggest that the production of specific anti GluN1 antibodies in vivo is the direct cause of the disease. However, the immunological mechanism of the upstream antibody is not clear. At present, the clinical diagnosis of GluN1 antibody is dependent on cerebrospinal fluid (CSF). The main clinical evaluation methods include clinical symptoms, modified Rankin score, The levels of cytokines in cerebrospinal fluid and serum of patients with anti NMDAR encephalitis were measured. The clinical significance of NMDAR encephalitis was analyzed. Methods: the cerebrospinal fluid (CSF) and serum samples were collected from 13 patients with anti NMDAR encephalitis and 6 patients with non-inflammatory control group. The levels of five cytokines, BAFF, APRILILILIL-6 and CXCL10, were detected by Elisa. The experimental data were statistically analyzed by SPSS IBM 20.0 software, and the mean values of cytokines in different disease groups, acute phase and remission stage were compared. The distribution of serum APRIL between the experimental group and the non-inflammatory control group was significantly different. After Sidak test, the levels of cytokines in cerebrospinal fluid (CSF) were higher than those in control group. With an upward trend, There was no statistical difference, The distribution of CXCL13 BAFF and IL-6 in cerebrospinal fluid (CSF) was significantly different between acute and remission patients (P0. 050, P0. 014, P0. 041). There was a significant difference in the distribution of BAFF and IL-6 between acute and remission patients. Age was correlated with cerebrospinal fluid (CXCL13) level. Cerebrospinal fluid (CSF) lymphocyte inflammation affected the level of IL-6, cerebrospinal fluid (CSF) CXCL10 was correlated with patients' age and mRS, and the level of CSF APRIL was not correlated with the clinical characteristics of patients. The level of cerebrospinal fluid BAFFFU IL-6 (CXCL10) was not correlated with the clinical characteristics of the patients. The titer of anti GluN1 antibody in cerebrospinal fluid was basically consistent with that of cerebrospinal fluid. In acute phase (immunotherapy), cerebrospinal fluid (CSF) CXCL13 rapidly returned to normal level. Conclusion: the intrathecal humoral immune response assisted by B cells may be the main immune mechanism against NMDAR encephalitis, except the intrathecal immune response. There was also systemic humoral immune activation. The cerebrospinal fluid (CSF) CXCL13, BAFF, IL-6 and serum BAFF were potential biomarkers for evaluating and observing the response to treatment in patients with NMDAR encephalitis. The level of cerebrospinal fluid (CSF) IL-6 was correlated with lymphocytic inflammation in cerebrospinal fluid (CSF). Age may affect the level of CXCL13.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R742.9

【相似文献】