Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

• Published in: BMC infectious diseases Vol. 8; no. 1; p. 104
• Main Authors: Das, Rina, Hammamieh, Rasha, Neill, Roger, Ludwig, George V, Eker, Steven, Lincoln, Patrick, Ramamoorthy, Preveen, Dhokalia, Apsara, Mani, Sachin, Mendis, Chanaka, Cummings, Christiano, Kearney, Brian, Royaee, Atabak, Huang, Xiao-Zhe, Paranavitana, Chrysanthi, Smith, Leonard, Peel, Sheila, Kanesa-Thasan, Niranjan, Hoover, David, Lindler, Luther E, Yang, David, Henchal, Erik, Jett, Marti
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.07.2008; BioMed Central; BMC
• Subjects: Analysis of Variance; Animals; Anthrax - genetics; Bacillus anthracis - immunology; Biological Warfare Agents; Care and treatment; Diagnosis; Environmental Exposure; Gene Expression; Gene Expression Profiling - methods; Genetic aspects; Genetic screening; Humans; Infection; Leukocytes, Mononuclear - immunology; Macaca mulatta; Methods; Oligonucleotide Array Sequence Analysis; Physiological aspects; Principal Component Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA - genetics; Sensitivity and Specificity; Time Factors; United States
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/1471-2334-8-104

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. 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. 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. 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.