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Case Western Reserve University Tuberculosis Research Unit
  Integrating research to combat the global TB epidemic
 
 

Pathway Analysis of Tuberculosis Pathogenesis

Sponsor U.S. National Institutes of Health (R01-HL096811)
(Principal Investigator - Catherine Stein, Ph.D., CWRU)

Type of Study

Observational

Design

Longitudinal family-based study - uses subjects in the Kawempe Community Health Study (KCHS)

Project Site

Uganda

Sample Size

1,400

Population

Adults with culture confirmed active tuberculosis and their household contacts

Study Period

Uses KCHS subjects enrolled starting in March 2004

Interactions with TBRU

This study utilizes stored buffy coat and PBMC samples from KCHS study participants. Collaborating investigators, utilizing shared JCRC laboratory infrastructure.

Goal of Study:

The goal of the study is to investigate host genetic and immunologic predictors of resistance to M. tuberculosis infection and progression from latent M. tuberculosis infection to active tuberculosis disease. The pathogenesis of TB will then be modeled using a structural equation modeling approach that accounts for relationships between individuals in a household.

Objectives of Study:
  1. To examine genetic influences on resistance to Mtb infection and progression from latent infection to active disease. This will be achieved by fine mapping chromosomal regions identified through a genome wide scan and analyzing specific genes identified through the genome scan as well as innate immunity pathway genes
  2. To characterize immunological variables associated with resistance to infection. This will be done by analyzing cytokine responses to three ligands that are recognized by the innate immune response during Mtb infection
  3. To model pathogenesis of TB using structural equation modeling (SEM). We have recently developed a method to utilize family data within a SEM framework, and as part of this study objective, we will produce software implementing this method that will be available for public use
Research Activities: