title: Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease.
abstract: BACKGROUND
  Enterovirus 71 (EV71) infection can lead to a rapidly progressing, life-threatening, and severe neurological disease in young children, including the development of human hand, foot, and mouth disease (HFMD). This study aims to further characterize the specific immunological features in EV71-mediated HFMD patients presenting with differing degrees of disease severity.
  
  
  METHODS
  Comprehensive cytokine and chemokine expression were broadly evaluated by cytokine antibody array in EV71-infected patients hospitalized for HFMD compared to Coxsackievirus A16-infected patients and age-matched healthy controls. More detailed analysis using Luminex-based cytokine bead array was performed in EV71-infected patients stratified into diverse clinic outcomes. Additionally, immune cell frequencies in peripheral blood and EV71-specific antibodies in plasma were also examined.
  
  
  RESULTS
  Expression of several cytokines and chemokines were significantly increased in plasma from EV71-infected patients compared to healthy controls, which further indicated that: (1) GM-CSF, MIP-1β, IL-2, IL-33, and IL-23 secretion was elevated in patients who rapidly developed disease and presented with uncomplicated neurological damage; (2) G-CSF and MCP-1 were distinguishably secreted in EV71 infected very severe patients presenting with acute respiratory failure; (3) IP-10, MCP-1, IL-6, IL-8, and G-CSF levels were much higher in cerebrospinal fluid than in plasma from patients with neurological damage; (4) FACS analysis revealed that the frequency of CD19(+)HLADR(+) mature B cells dynamically changed over time during the course of hospitalization and was accompanied by dramatically increased EV71-specific antibodies. Our data provide a panoramic view of specific immune mediator and cellular immune responses of HFMD and may provide useful immunological profiles for monitoring the progress of EV71-induced fatal neurological symptoms with acute respiratory failure.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.forename: Linghang
authors.initials: L
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Hu
authors.forename: Xianwen
authors.initials: X
authors.lastname: Ren
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Shaoxia
authors.initials: S
authors.lastname: Sun
authors.forename: Yufen
authors.initials: Y
authors.lastname: Li
authors.forename: Xinchun
authors.initials: X
authors.lastname: Chen
authors.forename: Xingwang
authors.initials: X
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D018925:Chemokines / Q000097:blood* / Q000134:cerebrospinal fluid; D002675:Child, Preschool; D004770:Enterovirus / Q000276:immunology; D029821:Enterovirus A, Human / Q000276:immunology*; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D007155:Immunologic Factors / Q000097:blood / Q000134:cerebrospinal fluid; D007223:Infant; D008297:Male; D009422:Nervous System Diseases / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000821:virology; D040081:Protein Array Analysis; D012720:Severity of Illness Index; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D018925:Chemokines; D007155:Immunologic Factors