HIV-1感染者ILC3s的变化及临床意义和埃博拉病毒病的临床诊治

发布时间：2018-05-24 08:19

本文选题：3型天然淋巴细胞 + 人类免疫缺陷病毒1型　；参考：《中国人民解放军医学院》2016年博士论文

【摘要】：第一部分HIV-1感染者ILC3s的变化及临床意义HIV-1感染后引起的异常免疫激活可导致抗病毒治疗后免疫重建失败、非艾滋相关事件发生率增加等临床难题。肠道黏膜屏障受损导致肠道微生物易位是可能的原因之一。鉴于3型天然淋巴细胞(group 3 innate lymphoid cells, ILC3s)在肠黏膜屏障功能的维持中发挥重要作用,为探讨ILC3s在HIV-1感染者中的变化及意义,本研究利用流式细胞术检测了HIV-1感染者外周血的ILC3s频率,发现HIV-1感染者外周血ILC3s频率降低.并与标志病情进展程度的病毒载量、CD4+T细胞数量和CD4/CD8比值相关;应用免疫组织化学方法检测HIV-1感染者肠黏膜组织中的ILC3s也较非HIV-1感染者减少;进一步研究ILC3s减少的机制发现,HIV-1感染者ILC3s表达CD95和活化caspase-3的水平升高,提示CD95/FasL途径介导的凋亡是ILC3s减少的原因之一;为研究ILC3s减少的临床意义,我们检测了反映微生物易位的脂多糖(LPS)及可溶性CD14 (sCD14)水平,发现HIV-1感染者外周血ILC3s频率与LPS和sCD14呈负相关,提示ILC3s的降低导致了肠道微生物易位。在第一部分中,我们认为HIV-1感染通过CD95/FasL途径介导细胞凋亡导致外周血和肠黏膜ILC3s的降低,从而导致肠黏膜屏障功能的破坏,引起微生物易位,以及后续的免疫激活等问题。第二部分埃博拉病毒病的临床诊治2013年12月起,西非地区爆发了历史上最大的一次埃博拉病毒病大流行,塞拉利昂是疫情最为严重的国家,为帮助该国处置疫情,解放军第302医院先后抽组5批次医疗队赴塞拉利昂首都弗里敦执行援非抗疫任务。本研究回顾性总结了确诊患者的临床资料,发现患者年龄分布以18-40岁为主,病死率随年龄、病毒载量升高而递增,生存时间随之递减,症状以发热、腹痛、腹泻等为主,腹泻、乏力和吞咽困难等在死亡组的发生率显著高于存活组。多因素分析发现年龄、病毒载量和有无腹泻症状与生存时间相关,年龄大、病毒载量高和有腹泻症状的属于高危患者,生存时间较短;在医疗资源紧张和缺乏特效抗病毒药物的条件下,将静脉补液等支持治疗手段优先用于这部分患者可能降低病死率。
[Abstract]:The changes of ILC3s in patients with HIV-1 infection and its clinical significance the abnormal immune activation caused by HIV-1 infection may lead to the failure of immune reconstruction after antiviral therapy and the increasing incidence of non-AIDS-related events and other clinical problems. One of the possible reasons for intestinal microbial translocation is intestinal mucosal barrier damage. In view of the important role of type 3 natural lymphocyte group 3 innate lymphoid cells, ILC3s in the maintenance of intestinal mucosal barrier function, in order to investigate the changes and significance of ILC3s in HIV-1 infected patients, the frequency of ILC3s in peripheral blood of HIV-1 infected patients was detected by flow cytometry. The frequency of ILC3s in peripheral blood of HIV-1 infected patients was decreased. The number of CD4 T cells and the ratio of CD4/CD8 were correlated with the viral load and the ratio of CD4/CD8, and the number of ILC3s in intestinal mucosa of HIV-1 infected patients was lower than that of non-HIV-1 infected patients. Further study on the mechanism of ILC3s reduction found that the level of ILC3s expression and activated caspase-3 increased in HIV-1 infected patients, suggesting that apoptosis mediated by CD95/FasL pathway is one of the causes of ILC3s decrease, and in order to study the clinical significance of ILC3s reduction, We detected the levels of lipopolysaccharide (LPS) and soluble CD14 (CD14) in peripheral blood of HIV-1 infected patients, and found that the frequency of ILC3s in peripheral blood was negatively correlated with LPS and sCD14, suggesting that the decrease of ILC3s resulted in intestinal microbial translocation. In the first part, we believe that HIV-1 infection mediated apoptosis through CD95/FasL pathway leads to the decrease of ILC3s in peripheral blood and intestinal mucosa, which leads to the destruction of intestinal mucosal barrier function, microbial translocation, and subsequent immune activation. The second part of the clinical diagnosis and treatment of Ebola virus disease since December 2013, the West African region has the largest Ebola epidemic in history, Sierra Leone is the most severely affected country, to help the country to deal with the epidemic. PLA 302 Hospital drew 5 batches of medical teams to Freetown, Sierra Leone, to carry out anti-African missions. The clinical data of the patients were summarized retrospectively. It was found that the age distribution of the patients was mainly 18-40 years old, the mortality increased with age, the viral load increased, the survival time decreased, the symptoms were fever, abdominal pain, diarrhea, etc. The incidence of fatigue and dysphagia was significantly higher in the death group than in the surviving group. Multivariate analysis showed that age, viral load and diarrhea symptoms were associated with survival time. The patients with high viral load and diarrhea symptoms were at high risk and had shorter survival time. Under the condition of shortage of medical resources and lack of special antiviral drugs, it is possible to reduce the mortality rate by using the support therapy such as intravenous fluid resuscitation in this group of patients.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R512.8;R512.91

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