EV71所致手足口病并发神经源性肺水肿免疫损伤的相关研究

【作者】 李伟；

【导师】 王静；

【作者基本信息】 青岛大学 ， 免疫学， 2015， 硕士

【摘要】 目的:观察重症和危重症EV71感染所致手足口病患儿血清细胞因子、免疫球蛋白、补体水平及外周血T淋巴细胞亚群的变化,探讨上述因素在EV71感染所致手足口病并发神经源性肺水肿免疫损伤中的作用。方法:将134例EV71感染的手足口病患儿根据临床症状分为三组:危重组(脑炎并发肺水肿、心肺衰竭者)共18例,重症组(单纯脑炎者)64例及普通组(单纯手足口病无并发症者)52例。对三组患儿采用散射比浊法测定血清免疫球蛋白Ig A、Ig G、Ig M和血清补体C3、C4含量;采用ELISA法检测血清IL-6、IL-10、TNF-α及IFN-γ含量;采用流式细胞术检测外周血CD3+、CD4+及CD8+T细胞的百分比。比较三组患儿所测的数值的差异,观察患儿免疫反应对病情的影响。结果:①Ig A和IgG含量的变化趋势相同:危重组和重症组之间差异无统计学意义(p>0.05),但两组较普通组明显降低,差异有统计学意义(p<0.05);Ig M含量:三组之间比较差异无统计学意义(p>0.05);②补体C3、C4含量变化趋势相同:在危重组中含量明显降低,与普通组和重症组相比,差异有统计学意义(p<0.05),重症组和普通组比较差异无统计学意义(p>0.05);③IL-6含量:危重组和重症组较普通组均升高,差异有统计学意义(p<0.05),但危重组和重症组之间差异无统计学意义(p>0.05);④IL-10含量:危重组较重症和普通两组明显升高,三组之间比较差异均有统计学意义(p<0.05);⑤IFN-γ含量:重症组较普通组,危重组较重症组均有明显升高,三组之间比较差异有统计学意义(p<0.05);⑥TNF-α含量:在危重组中水平明显降低,与重症组和普通组比较差异有统计学意义(p<0.05);重症组相对于普通组有升高趋势但差异无统计学意义(p>0.05);⑦CD3+T、CD4+T细胞百分比:在危重组含量明显低于重症组和普通组,差异有统计学意义(p<0.05);重症组较普通组明显升高,差异有统计学意义(p<0.05);⑧CD8+T细胞百分比:危重组和重症组之间差异不明显,但相比普通组都有明显升高,差异有统计学意义(p<0.05);⑨CD4+/CD8+比值:普通组和重症组变化不明显,差异无统计学意义(p>0.05),在危重组则降低明显近乎倒置,与重症组和普通组比较差异有统计学意义(p<0.05)。结论:①EV71感染所致手足口病并发神经源性肺水肿患者血清IL-10、TNF-α、IFN-γ水平的变化及外周血CD4+/CD8+比值的异常与疾病的危重化进程密切相关;②血清Ig A和Ig G以及补体C3、C4水平的降低可以在一定程度上反映疾病的严重程度;③本研究可为EV71感染所致手足口病并发神经源性肺水肿的临床诊断和治疗提供实验依据。更多还原

【Abstract】 Objective:To investigate the immune mechanism of neurogenic pulmonary edema complicated by enterovirus-71-related hand, foot and mouth disease(HFMD) by detecting the serum levels of cytokines, immunoglobulins, complements and changes of subgroups of T lymphocyte.Methods:According to the clinical symptoms and classification standards, children with HFMD caused by enterovirus-71 were divided into three groups, the critical group(18 cases with neurogenic pulmonary edema and cardiopulmonary failure),the severe group(64 cases with pure encephalitis without pulmonary edema) and the common group(52 cases without complications). Serum levels of immunoglobulins(Ig G, Ig A, and Ig M) and complements(C3 and C4) were detected by immunonehelomitery. And IL-6, IL-10, TNF-α and IFN-γ levels were detected by ELISA. Flow cytometry was used to analyze the percentage of CD3+、CD4+ and CD8+ T cell in leukomonocyte suspensions. Results were analyzed to determine the influence of immune response to children’s condition.Results:① Serum levels of Ig A and Ig G of the critical group and the severe group were drastically lower than the common group with statistical significance(p<0.05). However the difference between the critical group and the severe group were not statistically significant. Levels of Ig M among the three groups were not statistically different(p>0.05). ② Serum levels of C3 and C4 of the critical group were significantly lower than the severe group and the common group(p<0.05). However the difference between the severe group and the common group was not statistically significant. ③ IL-6 levels of the critical group and the severe group were significantly higher than the common group(p<0.05),while the difference between the critical group and the severe group was not statistically significant. ④ IL-10 level of the critical group was higher than the severe group, and the severe group was higher than the common group. All the differences among the three groups were statistically significant(p<0.05). ⑤ The change trend of IFN-γ was similar to that of IL-10, with statistical significance among the three groups(p<0.05). ⑥ TNF-α level of the critical group was lower than the severe group and the common group(p<0.05). However the difference between the severe group and the common group was not statistically significant. ⑦ The percentages of CD3+ and CD4+ T cells of the critical group were obviously lower than the severe group and the common group with statistical significance(p<0.05). ⑧ The percentage of CD8+ T cells of the critical group was slightly lower than the severe group with no statistical significance(p>0.05). However both the critical group and the severe group were statistically higher than the common group(p<0.05). ⑨ The ratio of CD4+ to CD8+ T cells of the critical group was nearly reversed, significantly decreased than the severe group and the commongroup(p<0.05), while the difference between the severe group and the common group was not statistically significant(p>0.05).Conclusion:①Serum levels of IL-10、TNF-α and IFN-γ and the ratio of CD4+ to CD8+ T cells in children with HFMD caused by EV71 in complication with neurogenic pulmonary edema are closely associated with the severity and progression of disease.② Decrease of serum levels of Ig A, Ig G, complement C3 and C4 is, to some extent, related to the severity of disease.③Our research provides experimental basis for clinical diagnosis and treatment of HFMD caused by EV71 in complication with neurogenic pulmonary edema.更多还原