title: Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells.
abstract: BACKGROUND
  Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.
  
  
  METHODS
  To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.
  
  
  RESULTS
  We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin.
  
  
  CONCLUSIONS
  Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.
authors.affiliation: Division of Pathology, Walter Reed Army Institute of Research, Silver Spring, MD, USA. dasr2@nhlbi.nih.gov
authors.forename: Rina
authors.initials: R
authors.lastname: Das
authors.forename: Rasha
authors.initials: R
authors.lastname: Hammamieh
authors.forename: Roger
authors.initials: R
authors.lastname: Neill
authors.forename: George V
authors.initials: GV
authors.lastname: Ludwig
authors.forename: Steven
authors.initials: S
authors.lastname: Eker
authors.forename: Patrick
authors.initials: P
authors.lastname: Lincoln
authors.forename: Preveen
authors.initials: P
authors.lastname: Ramamoorthy
authors.forename: Apsara
authors.initials: A
authors.lastname: Dhokalia
authors.forename: Sachin
authors.initials: S
authors.lastname: Mani
authors.forename: Chanaka
authors.initials: C
authors.lastname: Mendis
authors.forename: Christiano
authors.initials: C
authors.lastname: Cummings
authors.forename: Brian
authors.initials: B
authors.lastname: Kearney
authors.forename: Atabak
authors.initials: A
authors.lastname: Royaee
authors.forename: Xiao-Zhe
authors.initials: XZ
authors.lastname: Huang
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Paranavitana
authors.forename: Leonard
authors.initials: L
authors.lastname: Smith
authors.forename: Sheila
authors.initials: S
authors.lastname: Peel
authors.forename: Niranjan
authors.initials: N
authors.lastname: Kanesa-Thasan
authors.forename: David
authors.initials: D
authors.lastname: Hoover
authors.forename: Luther E
authors.initials: LE
authors.lastname: Lindler
authors.forename: David
authors.initials: D
authors.lastname: Yang
authors.forename: Erik
authors.initials: E
authors.lastname: Henchal
authors.forename: Marti
authors.initials: M
authors.lastname: Jett
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000881:Anthrax / Q000235:genetics; D001408:Bacillus anthracis / Q000276:immunology*; D054045:Biological Warfare Agents; D004781:Environmental Exposure; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008253:Macaca mulatta; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D054045:Biological Warfare Agents; D012313:RNA