title: Biomarkers Can Identify Pulmonary Tuberculosis in HIV-infected Drug Users Months Prior to Clinical Diagnosis.
abstract: BACKGROUND
  Current diagnostic tests cannot identify which infected individuals are at risk for progression to tuberculosis (TB). Our aim was to identify biomarkers which can predict the development of TB prior to clinical diagnosis.
  
  
  METHODS
  In a retrospective case-control study, RNA of 14 HIV-infected drug users obtained before TB diagnosis (cases) and of 15 who did not develop TB (controls) was analyzed for the expression of 141 genes by dcRT-MLPA followed by Lasso regression analysis.
  
  
  RESULTS
  A combined analysis of IL13 and AIRE had the highest discriminatory power to identify cases up to 8 months prior to clinical diagnosis. Cases expressing IL13 had a gene expression pattern strongly enriched for type I IFN related signaling genes, suggesting that these genes represent processes that contribute to TB pathogenesis.
  
  
  CONCLUSIONS
  We here demonstrated that biomarkers, such as IL13-AIRE, can identify individuals that progress to TB within a high risk population, months prior to clinical diagnosis.
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ; Center for Infections and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rosa
authors.initials: R
authors.lastname: Sloot
authors.affiliation: Center for Infections and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ; Department of Infectious Diseases, Public Health Service, Amsterdam, The Netherlands.
authors.forename: Maarten F
authors.initials: MF
authors.lastname: Schim van der Loeff
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Erik W
authors.initials: EW
authors.lastname: van Zwet
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mariëlle C
authors.initials: MC
authors.lastname: Haks
authors.affiliation: Department of Infectious Diseases, Public Health Service, Amsterdam, The Netherlands.
authors.forename: Sytze T
authors.initials: ST
authors.lastname: Keizer
authors.affiliation: Department of Infectious Diseases, Public Health Service, Amsterdam, The Netherlands ; Department of Medical Microbiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Scholing
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ; Center for Infections and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ; Department of Infectious Diseases, Public Health Service, Amsterdam, The Netherlands.
authors.forename: Martien W
authors.initials: MW
authors.lastname: Borgdorff
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Joosten
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications; D006801:Humans; D007370:Interferon Type I / Q000097:blood*; D018793:Interleukin-13 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D019966:Substance-Related Disorders / Q000097:blood* / Q000150:complications; D014157:Transcription Factors / Q000097:blood*; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000209:etiology; D000096927:AIRE Protein
chemical_list: D015415:Biomarkers; D007370:Interferon Type I; D018793:Interleukin-13; D014157:Transcription Factors; D000096927:AIRE Protein
keywords: Gene expression; HIV; Host biomarkers; Tuberculosis; dcRT-MLPA