EB病毒相关性噬血细胞综合征患儿EB病毒潜伏膜蛋白1及Th1细胞因子的表达及其意义

Expression of EB virus latent membrane protein 1 and Th1 cytokines in children with EB virus-associated hemophagocytic syndrome and its significance

目的:分析EB病毒相关性噬血细胞综合征(EB virus-associated hemophagocytic syndrome,EBVAHS)患儿EB病毒潜伏膜蛋白1(latent membrane protein 1,LMP1)、辅助性T细胞1(helper T cell1,Th1)细胞因子的表达水平及其与疗效的关系。方法:抽取郑州大学附属儿童医院儿科2014年2月至2018年1月收治的116例EB病毒感染患儿为研究对象,分为单核细胞增多症(infect iousmononucleosis,IM)组与EBV-AHS组,其中IM 66例,EBV-AHS 50例。EBV-AHS组按照国际组织细胞协会推荐的HLH-2004方案给予治疗,于治疗4周后评定近期疗效。另选取同期体检的健康儿童30例作为对照组。对照组于体检时、IM组于确诊时、EBV-AHS组于治疗前、治疗后采血,检测血清LMP1抗体表达及Th1细胞因子水平。结果:与对照组相比,IM组和EBV-AHS组患儿确诊时血清LMP1抗体、白介素(IL)-2、干扰素(IFN)-γ及肿瘤坏死因子(TNF)-α水平显著增高,差异有统计学意义(P<0.05)。IM组和EBV-AHS组患儿血清LMP1抗体,IL-2,IFN-γ,TNF-α水平差异亦有统计学意义(P<0.05)。治疗后EBV-AHS组50例患儿中,疾病缓解者17例(34.00%),有效者22例(44.00%),余下11例(22.00%)疾病活动。疾病缓解者、有效者血清LMP1抗体,IL-2,IFN-γ,TNF-α水平明显较治疗前降低(P<0.05),而疾病活动者血清LMP1抗体,IL-2,IFN-γ,TNF-α水平较治疗前无明显改善(P>0.05);且疾病缓解者、有效者、疾病活动者血清LMP1抗体,IL-2,IFN-γ,TNF-α水平均依次升高,差异有统计学意义(P<0.05)。结论:EBV-AHS患儿血清LMP1抗体表达及Th1细胞因子水平较IM患儿及正常儿童显著升高,且其与疗效密切相关。

Objective: To analyze the expression levels of Epstein-Barr (EB) virus latent membrane protein 1 (LMP1) and helper T cell 1 (Th1) cytokines in children with EB virus-associated hemophagocytic syndrome (EBV-AHS) and their relationship with the curative effect. Methods: A total of 116 EB virus infected children who were admitted to the department of pediatrics during the period from February 2014 to January 2018 were selected as the study subjects, including 66 cases of the infectious mononucleosis (IM)(IM group) and 50 cases of the EBV-AHS (EBV-AHS group). EBV-AHS group were treated according to the HLH-2004 regimen recommended by the International Association for Cellular Society. The short-term curative effect was evaluated after 4 weeks of treatment. Another 30 healthy children admitted to the hospital during the same period were selected as the control group. The blood samples of children in the control group was collected during the physical examination, while those of the IM group were collected at confirmed diagnosis and those of the case group were collected before and after treatment to detect the expression of serum LMP1 antibody and levels of Th1 cytokines. Results: Compared with the control group, levels of serum LMP1 antibody, interleukin (IL)-2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were significantly higher in IM group and EBV-AHS group at confirmed diagnosis (P<0.05), with statistically significant differences between IM group and EBV-AHS group (P<0.05). After treatment, of the 50 patients in EBV-AHS group, 17 patients (34.00%) were relieved, 22 patients (44.00%) were effectively treated, and 11 patients (22.00%) had activity of disease. The levels of serum LMP1 antibody, IL-2, IFN-γ and TNF-α in relieved patients and effectively treated patients were significantly lower than those before treatment (P<0.05). The levels of serum LMP1 antibody, IL-2, IFN-γ and TNF-α in patients with activity of disease were not significantly improved(P>0.05). The levels of serum LMP1 antibody, IL-2, IFN-γ and TNF-α were all increased in the relieved patients, the effectively treated patients, and the patients with activity of disease (P<0.05). Conclusion: The expression of LMP1 antibody and levels of Th1 cytokines in children with EBV-AHS are significantly higher than those in children with IM and normal children, and they were closely related to the curative effect.