title: Proteome demonstration of alpha-1-acid glycoprotein and alpha-1-antichymotrypsin candidate biomarkers for diagnosis of enterovirus 71 infection.
abstract: BACKGROUND
  Human enterovirus 71 (EV71) is the major causative agents of hand-foot-and-mouth disease and frequently associated with severe complications such as encephalitis and death. Understanding the host response following enteroviral infection may facilitate the development of biomarkers for EV71 infections.
  
  
  METHODS
  We implemented two-dimensional gel electrophoresis technology on proteins prepared from serum obtained from 4 mild and 4 severe cases of EV71 infections and 4 healthy control children, to investigate the differentially expressed proteins. The differential expressed proteins were further identified with liquid chromatography-mass spectrometry/mass spectrometry analysis and western blotting validation.
  
  
  RESULTS
  A total of 27 differentially expressed proteins were picked and identified with liquid chromatography-mass spectrometry/mass spectrometry. Of the 27 identified proteins, 6 proteins were up-regulated in the mild-infected and severe EV71-infected patients in comparison to the healthy control group. Two proteins, alpha-1-acid-glycoprotein (AGP1) and alpha-antichymotrypsin (AACT), were not detected in the EV71-infected patients, but appeared in the control patient. Western blotting analysis demonstrated that AGP1 and AACT proteins were negatively associated with the clinical severity of EV71 infection. Similarly, both of the proteins were not detected in the secretion medium from the EV71-infected neuroblastoma cells, but detected in the mock-infected cells, suggesting that differentially expressed AGP1/AACT protein levels are in response to EV71 infections.
  
  
  CONCLUSIONS
  Two candidate proteins AGP1 and AACT, whose expression levels were reduced under the EV71 infection pathological condition, provide useful source of information for potential diagnostic biomarkers of EV71 infection in children.
authors.affiliation: From the *Department of Biomedical Sciences, †Research Center for Emerging Viral Infections, ‡Department of Medical Biotechnology and Laboratory Sciences College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; §Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan; and ¶Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial and Children's Hospital, Linkuo, Taiwan.
authors.forename: Robert Y L
authors.initials: RY
authors.lastname: Wang
authors.forename: Rei-Lin
authors.initials: RL
authors.lastname: Kuo
authors.forename: Sih-Min
authors.initials: SM
authors.lastname: Yen
authors.forename: Chien-Hsun
authors.initials: CH
authors.lastname: Chu
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Wu
authors.forename: Yhu-Chering
authors.initials: YC
authors.lastname: Huang
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D029821:Enterovirus A, Human / Q000302:isolation & purification*; D004769:Enterovirus Infections / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009961:Orosomucoid / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D009961:Orosomucoid; D020543:Proteome; D000514:alpha 1-Antichymotrypsin