Fu Dan, Li Cheng-rong, He Yan-xia, Zu Ying, Cao De-zhi, Wang Guo-bing, Deng Ji-kui, Wang He-ping
Department of Emergency Medicine, Shenzhen Children's Hospital, Shenzhen 518026, China.
Zhonghua Er Ke Za Zhi. 2009 Nov;47(11):829-34.
To investigate the association of changes in immune function with enterovirus 71 (EV71) cases with different severity of the disease.
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 CD4+CD25+ Foxp3high regulatory T cells (Treg cells) and Th17 cells, cytokines (IL-1beta, TNF-alpha, IL-10, TGF-beta, IL-6, IL-17A), evaluated the mRNA levels of Foxp3 and ROR-gammat, and serum immunoglobulin and complements.
(1) Serum concentrations of IL-1beta and TNF-alpha 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-alpha 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-beta gradually decreased with the aggravation of the disease, while the proportion of Th17 cells, serum concentrations of IL-17A, mRNA level of ROR-gammat, and IL-6 gradually increased with the aggravation.
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 EV71 infection should emphasize different methods at different stage and individualization.
探讨免疫功能变化与不同疾病严重程度的肠道病毒71型(EV71)病例之间的关联。
本研究纳入了46例EV71感染患者和12例年龄匹配的健康儿童。根据肠道病毒71型感染的危急程度将患者分为四组:手足口病(HFMD);中枢神经系统疾病(CNSD);自主神经系统失调(ANSD)和肺水肿(PE)。我们分析了CD14+单核细胞HLA-DR表达、淋巴细胞免疫表型、CD4+CD25+ Foxp3高调节性T细胞(Treg细胞)和Th17细胞的比例、细胞因子(IL-1β、TNF-α、IL-10、TGF-β、IL-6、IL-17A),评估了Foxp3和ROR-γt的mRNA水平以及血清免疫球蛋白和补体。
(1)轻度病例血清IL-1β和TNF-α浓度升高,而重度病例下降,且PE组更低(P<0.05)。血清IL-10浓度和IL-10/TNF-α比值随疾病加重逐渐升高,且PE组更高(P<0.05)。(2)循环CD14+单核细胞HLA-DR表达、CD3+T细胞、CD4+T细胞、CD8+T细胞和NK细胞逐渐减少,且PE组更低(P<0.05)。四组之间B细胞、免疫球蛋白和补体无显著差异。(3)CD4+CD25+ Foxp3高Treg细胞比例、Foxp mRNA水平和血清TGF-β浓度随疾病加重逐渐降低,而Th17细胞比例、血清IL-17A浓度、ROR-γt mRNA水平和IL-6随疾病加重逐渐升高。
免疫功能随疾病不同阶段而变化。轻度病例呈现全身炎症反应综合征状态,而危重症病例呈现代偿性抗炎反应综合征或混合拮抗反应状态。对EV71感染患者的免疫调节治疗应在不同阶段强调不同方法并个体化。