Ancillary T Cell Based Studies in SPIROMICS
| Status: | Recruiting |
|---|---|
| Conditions: | Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 40 - 80 |
| Updated: | 4/21/2016 |
| Start Date: | February 2012 |
| End Date: | February 2016 |
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).
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).
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.
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.
Inclusion Criteria:
- Over 4o, former or active smokers
Exclusion Criteria:
- HIV infection, chronic hepatitis B and C, immune suppressive medications.
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