肠道病毒71型感染患儿免疫功能探讨

Changes of immune function in patients with enterovirus 71 infection

目的探讨肠道病毒71型（EV71）感染患儿免疫功能变化与病情程度的关系。方法患儿46例，健康同龄儿童12例，根据病情由轻到重将患儿分为4组：手足口病组11例、中枢神经系统病变组20例、中枢神经系统病变伴自主神经功能失凋组10例、神经源性肺水肿组（pulmonaryedema，PE组）5例。进行下述检测：CD14＋单核细胞人类白细胞DR抗原（HLA—DR）表达率、淋巴细胞免疫分型、CIM＋CD25＋Foxp3high调节性T细胞（regulatoryTcells，Tregcells）及THl7细胞比例；白细胞介素1B（IL-1β）、肿瘤坏死因子仪（TNF—α、白细胞介素10（IL-10）、转录生长因子B（TGF—β）、白细胞介素6（IL-6）、白细胞介素17A（IL-17A）血浓度；CD4＋T细胞Foxp3、ROR-叩基因表达；血清免疫球蛋白及补体等。结果（1）前炎症细胞因子TNF—α及IL-1B在轻症患儿中增高，随病情加重而下降，PE组明显降低（P〈0．05）；抗炎细胞因子IL—10及1L-10／TNF—α比值随病情加重增高，PE组增高明显（P〈0．05）。（2）HLA—DR、CD3＋T细胞、CD4＋T细胞、CD8＋T细胞、NK细胞随病情加重呈现逐步下降趋势，PE组下降最为明显（P〈0．05）。各组间B淋巴细胞及抗体差异无统计学意义。（3）Treg细胞比例、转录因子Foxp3mRNA及诱导因子TGF-13血浓度随病情加重降低，而TH17细胞比例、IL-17A血浓度、转录因子ROR-7tmRNA及诱导因子IL-6血浓度随病情加重升高。结论EV71感染患儿机体免疫功能随病情程度而变化，轻症患儿处于全身炎症反应状态，重症或危重症病例处于代偿性抗炎症反应或混合性拮抗反应状态，对EV71感染的免疫调控治疗应强调分阶段、个体化。

Objective To investigate the association of changes in immune function with enterovirus 71 （EV71） cases with different severity of the disease. Method Forty-six EV71-infected patients and 12 age-matched healthy children were enrolled in this study. The patients were divided into four groups according to critical degree of enterovirus 71 infection： hand-foot-and-mouth disease （HFMD）; central nervous system disease （CNSD） ; autonomic nervous system dysregulation （ANSD） and pulmonary edema （PE）. We analyzed CD14 ＋ monocyte HLA-DR expression, lymphocyte immunophenotypes, the proportion of CIM ＋ CD25 ＋ Foxp3high regulatory T cells （Treg cells） and Thl7 cells, cytokines （ IL-Iβ, TNF-α, IL-10, TGF-β, IL-6, IL-17A ） , evaluated the mRNA levels of Foxp3 and ROR-γt, and serum immunoglobulin and complements. Result （1） Serum concentrations of IL-1β and TNF-α elevated in mild cases, while declined in severe cases, and were lower in PE group （P 〈 0. 05）. Serum concentrations of IL-10 and IL- 10/TNF-α ratio gradually raised with the aggravation of the disease, and higher in PE group （P 〈0. 05）. （2） Circulating CD14＋ monocyte HLA-DR expression, CD3＋T cells, CD4＋T cells, CD8＋T cells, and NK cells gradually decreased, and lower in PE group （ P 〈 0. 05 ）. There was no significant difference in B cells, immunoglobulin and complement among the four groups. （3） The proportion of CD4＋ CD25 ＋ Foxp3high Treg cells, mRNA level of Foxp, and serum concentrations of TGF-β gradually decreased with the aggravation of the disease, while the proportion of Thl7 cells, serum concentrations of IL-17A, mRNA level of ROR-γt, and IL-6 gradually increased with the aggravation. Conclusion Immune function changed with different illness phases. The mild cases presented systemic inflammatory response syndrome status, while critically ill cases presented compensatory anti-inflammatory response syndrome or mixed antagonist response status. Immunoregulatory treatment of patients with EVT1 infection should emphasize different methods at different stage and individualization.