PI: Jacques Banchereau
Funding Organization: National Institute of Allergy and Infectious Diseases
Project Start: July 1, 2006
Project End: June 30, 2008
Abstract:
Aim: To identify blood transcriptional markers associated with pathogenesis and disease progression in patients with HIV infection.
Longitudinal blood samples obtained from a cohort of 60 patients with recent HIV infection will be analyzed using high-density gene expression microarrays.
Detailed clinical information collected for each patient will be integrated along with experimental results into a relational database.
We will 1) identify disease-associated blood transcriptional patterns by comparing expression profiles obtained for patients with HIV and uninfected controls,
and 2) identify markers of disease activity by correlating changes in gene expression to the patient clinical phenotype.
Hypothesis: HIV infection is associated with perturbations of blood gene expression profiles that can be detected by DNA microarray analysis. Monitoring transcriptional perturbation in patients with HIV on a genome-wide scale will inform us on mechanisms of pathogenesis and lead to the identification of clinically relevant markers.
Rationale: Studying transcriptional changes in the blood of patients with HIV infection will serve two purposes: 1) It will advance our understanding of mechanisms of disease pathogenesis. Insight gained from microarray-based patient studies led us to the discovery of the role of Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis.
We have mapped transcriptional changes occurring on a genome-wide scale in patients with autoimmune diseases, cancer and acute infections. Similarly, comparing expression profiles obtained for patients with HIV and uninfected controls will permit us to identify interpretable disease-associated blood transcriptional patterns.
2) Studying transcriptional changes in the blood of patients with HIV infection could also lead to the identification of clinically relevant disease markers. As a proof of concept, leukocyte transcriptional profiling studies carried out at BIIR have identified diagnostic signatures of acute infection with influenza virus, respiratory syncytial virus, Escherichia coli, Staphylococcus aureus and Streptococcus pneumoniae.
Furthermore we characterized blood transcriptional markers for the differential diagnosis of patients with Systemic Onset Juvenile Idiopathic Arthritis, and most recently developed and validated a multivariate microarray transcriptional indicator of disease severity in SLE patients (microarray transcriptional score).
In the context of the proposed study such an approach would permit us to identify transcriptional correlates of disease activity in the blood of patients with HIV.
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