Ancillary T Cell Based Studies in SPIROMICS
Condition: Smoke Induced Lung Disease
MeSH terms: Lung Diseases
Study type: Observational

Summary: 
      The long-term objectives of this ancillary application are to characterize a subpopulation of
      smokers with auto-reactive T cell response, to validate immunodiagnostic assays that could
      detect emphysema, and to find molecular signatures for pathogenic T cell development in a
      well-characterized cohort participating in SPIROMICS (UCSF center).
    

Detailed description: 
      One of the major medical challenges facing us is that susceptibility to smoking-induced lung
      diseases varies greatly and essentially precludes our ability to predict which smokers will
      develop emphysema. Because the SPIROMICS study is designed to phenotype a large and
      heterogeneous group of smokers, we have chosen this cohort to identify the subpopulation who
      have auto-reactive T cells, as this may represent a contributing mechanism in the development
      of emphysema, which may need alternative therapies, and may represent a group of patients who
      will have progressive disease despite smoking cessation. In Aim 1, we will prospectively
      determine the presence of auto-reactive T cell responses as determined by increased cytokine
      release in 180 ever-smokers with and without emphysema; in Aim 2 we will focus on the
      longitudinal aspect of the factors that could predispose development of auto-reactive T cells
      in the population at risk. These studies form the prerequisite basis for developing
      additional novel immune-based diagnostic and therapeutic strategies in human emphysema. The
      short-term objectives outlined here are based on our preliminary data, and provide the
      necessary platform that will be used to answer the following urgent questions: i) in a
      distinct prospective cohort of ever smokers, can auto-reactive T cells predict the presence
      of radiographic emphysema? ii) Can we identify unique and persistent transcriptional
      signature(s) that are associated with autoimmune emphysema? The observational and
      longitudinal design of SPIROMICS allows for detailed assessment of the association between
      emphysema as the primary clinical endpoints and could validate the novel T cell specific
      immunodiagnostic potential that has been developed in our laboratory. We propose to explore
      the role of autoimmunity as a contributing mechanism in the development of emphysema with the
      additional aim of bringing current technologies to bear on clinical and future diagnostic
      tests. PUBLIC HEALTH RELEVANCE: We have discovered specific autoreactive T cells in
      ever-smokers with emphysema and there is growing evidence linking these particular effector
      cells with the pathophysiology of smoking related lung disease. Our proposed studies are
      important because they will provide new diagnostic and prognostic assays (e.g. gamma-6-Spot,
      based on Th1 and Th17 cytokines) in ever-smokers who have, or are at risk of developing
      emphysema.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Former or current smokers, over 40 years of age recruited in SPIROMICS at UCSF
      
Biospecimen description: 
      PBMC
    
Keywords: COPD, chronic obstructive pulmonary disease, emphysema