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Open Access Research article

The significance of Notch ligand expression in the peripheral blood of children with hand, foot and mouth disease (HFMD)

Zhen Jiang Bai1, Yi Ping Li2, Jie Huang2, Yong Jun Xiang3, Chun Yu Lu3, Xiao Xing Kong4, Jian Mei Tian4, Jiang Huai Wang5 and Jian Wang3*

Author Affiliations

1 Pediatric Intensive Care Unit, Affiliated Children's Hospital, Soochow University, Suzhou, China

2 Institute of Pediatric Research, Affiliated Children's Hospital, Soochow University, Suzhou, China

3 Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China

4 Department of the Infectious Disease, Affiliated Children’s Hospital, Soochow University, Suzhou, China

5 Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland

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BMC Infectious Diseases 2014, 14:337  doi:10.1186/1471-2334-14-337

Published: 17 June 2014



Hand, foot and mouth disease (HFMD), a virus-induced infectious disease that usually affects infants and children, has an increased incidence in China in recent years. This study attempted to investigate the role of the Notch signaling pathway in the pathogenesis of HFMD.


Eighty-two children diagnosed with HFMD were enrolled into this study. The HFMD group was further divided into the uncomplicated HFMD and HFMD with encephalitis groups. The control group included 40 children who underwent elective surgery for treatment of inguinal hernias.


Children with HFMD displayed significantly reduced CD3+, CD3+CD4+ and CD3+CD8+ cell subsets, but substantially enhanced CD3CD19+ cell subset (p < 0.05 versus control subjects). The expression levels of Notch ligands Dll1 and Dll4 in the peripheral blood of the HFMD group were significantly higher than those in the control group (p < 0.05). There were statistically significant differences in CD3+, CD3+CD4+ and CD3CD19+ cell subsets, but not in Notch ligand expression, between the uncomplicated HFMD and HFMD with encephalitis groups. Dll4 expression in HFMD subjects correlated negatively with the CD3+ and CD3+CD8+ cell subsets (p < 0.05), but positively with the CD3CD19+ cell subset (p < 0.05). Furthermore, Dll4 expression in HFMD with encephalitis subjects correlated positively with total white blood cell (WBC) counts and total protein contents in cerebrospinal fluid (CSF) (p < 0.05).


The Notch ligand Dll4 exhibits a strong correlation with the CD3+, CD3+CD8+ and CD3CD19+ cell subsets in children with HFMD, indicating that the Notch signaling may be involved in the development of HFMD by affecting the number and status of peripheral lymphocytes.

Notch signaling; Subsets of T lymphocytes; Hand; Foot and mouth disease; Children