title: The discovery and identification of a candidate proteomic biomarker of active tuberculosis.
abstract: BACKGROUND
  Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB.
  
  
  METHODS
  The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels.
  
  
  CONCLUSIONS
  A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Liu
authors.forename: Tingting
authors.initials: T
authors.lastname: Jiang
authors.forename: Liliang
authors.initials: L
authors.lastname: Wei
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Yang
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Dandan
authors.initials: D
authors.lastname: Xu
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Chen
authors.forename: Fuquan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Institute of Cell Biology, Zhejiang University School of Medicine, 388, Yuhangtang Road, Hangzhou 310058, P,R, China. lijichen@zju.edu.cn.
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D014376:Tuberculosis / Q000097:blood* / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005340:Fibrinogen