手足口病患儿外周血单个核细胞Notch配体的表达及其意义

The Expression and Significance of Notch Ligands in the Peripheral Blood Mononuclear Cells in Children with Hand, Foot and Mouth Disease （HFMD）

目的：了解Notch信号通路在手足口病发病中的作用。方法2012年6月-2012年12月苏州大学附属儿童医院感染病房和儿科重症监护病房收住的82例手足口病患儿，设为手足口病组，根据其临床表现和实验室结果分为单纯组和脑炎组，对照组为外科腹股沟斜疝择期手术患儿40例，将其流行病学、临床理化特征、外周血免疫细胞水平和Notch配体水平进行分析比较。结果手足口病组患儿具有更低的外周血CD3＋细胞、CD3＋CD4＋细胞和CD3＋CD8＋细胞水平，更高的CD3-CD19＋细胞水平（P＜0.05）；手足口病组外周血单个核细胞Notch配体Dll1和Dll4表达显著高于对照组（P＜0.05），而单纯组和脑炎组之间差异无统计学意义；外周血单个核细胞Dll4表达和CD3＋、CD3＋CD8＋淋巴细胞表达呈负相关（P＜0.05），与CD3-CD19＋淋巴细胞表达呈正相关（P＜0.05）；外周血单个核细胞Dll4表达与脑脊液中WBC总数和总蛋白含量（S-TP）呈正相关（P＜0.05）。结论 Notch信号通路可能参与手足口病的发病；Notch配体Dll4与外周血CD3＋、CD3＋CD8＋和CD3-CD19＋淋巴细胞有较强的相关性，可能通过影响这些免疫细胞的数量和状态从而影响疾病的预后。

Objective To investigate the role of the Notch signaling pathway in the pathogenesis of HFMD. Methods 82 children with HFMD were enrolled in this study. The HFMD group was further divided into uncomplicated HFMD group and HFMD with encephalitis group. The control group is 40 children who underwent elective surgery for treatment of inguinal hernias. Results Children with HFMD showed significantly reduced CD3＋, CD3＋CD4＋and CD3＋CD8＋cell subsets, but significantly enhanced CD3-CD19＋cell subset （P〈0.05 versus control subjects）. The expression of Notch ligands Dll1 and Dll4 in the peripheral blood mononuclear cells of the HFMD group were significantly higher than those in the control group （P〈0.05）. There were significant differences in CD3＋, CD3＋CD4＋and CD3-CD19＋cell subsets, but not in the Notch ligands expression, between the uncomplicated HFMD and HFMD with encephalitis groups. Dll4 expression in HFMD children correlated negatively with the CD3＋and CD3＋CD8＋cell subsets （P〈0.05）, while positively with the CD3-CD19＋cell subset （P〈0.05）. Furthermore, Dll4 expression in HFMD with encephalitis children correlated positively with total white blood cell （WBC） number and total protein concentration in cerebrospinal fluid （CSF） （P〈0.05）. Conclusion The Notch ligand Dll4 shows a strong correlation with the CD3＋, CD3＋CD8＋and CD3-CD19＋cell subsets in children with HFMD, which indicates that the Notch signaling may be involved in the development of HFMD by affecting the number and status of human peripheral lymphocytes.