title: Novel biomarkers distinguishing active tuberculosis from latent infection identified by gene expression profile of peripheral blood mononuclear cells.
abstract: BACKGROUND
  Humans infected with Mycobacterium tuberculosis (MTB) can delete the pathogen or otherwise become latent infection or active disease. However, the factors influencing the pathogen clearance and disease progression from latent infection are poorly understood. This study attempted to use a genome-wide transcriptome approach to identify immune factors associated with MTB infection and novel biomarkers that can distinguish active disease from latent infection.
  
  
  RESULTS
  Using microarray analysis, we comprehensively determined the transcriptional difference in purified protein derivative (PPD) stimulated peripheral blood mononuclear cells (PBMCs) in 12 individuals divided into three groups: TB patients (TB), latent TB infection individuals (LTBI) and healthy controls (HC) (n = 4 per group). A transcriptional profiling of 506 differentially expressed genes could correctly group study individuals into three clusters. Moreover, 55- and 229-transcript signatures for tuberculosis infection (TB&LTBI) and active disease (TB) were identified, respectively. The validation study by quantitative real-time PCR (qPCR) performed in 83 individuals confirmed the expression patterns of 81% of the microarray identified genes. Decision tree analysis indicated that three genes of CXCL10, ATP10A and TLR6 could differentiate TB from LTBI subjects. Additional validation was performed to assess the diagnostic ability of the three biomarkers within 36 subjects, which yielded a sensitivity of 71% and specificity of 89%.
  
  
  CONCLUSIONS
  The transcription profiles of PBMCs induced by PPD identified distinctive gene expression patterns associated with different infectious status and provided new insights into human immune responses to MTB. Furthermore, this study indicated that a combination of CXCL10, ATP10A and TLR6 could be used as novel biomarkers for the discrimination of TB from LTBI.
authors: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors: Chanyi
authors: C
authors: Lu
authors: Jing
authors: J
authors: Wu
authors: Honghai
authors: H
authors: Wang
authors: Sen
authors: S
authors: Wang
authors: Ni
authors: N
authors: Diao
authors: Feifei
authors: F
authors: Wang
authors: Yan
authors: Y
authors: Gao
authors: Jiazhen
authors: J
authors: Chen
authors: Lingyun
authors: L
authors: Shao
authors: Xinhua
authors: X
authors: Weng
authors: Ying
authors: Y
authors: Zhang
authors: Wenhong
authors: W
authors: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D014376:Tuberculosis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers