Ancillary T Cell Based Studies in SPIROMICS

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).

Study Overview

• Status: Completed
• Conditions: Smoke Induced Lung Disease

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.

• Study Type: Observational
• Enrollment (Actual): 175

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Ucsf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Former or current smokers, over 40 years of age recruited in SPIROMICS at UCSF

Description

Inclusion Criteria:

• Over 4o, former or active smokers

Exclusion Criteria:

• HIV infection, chronic hepatitis B and C, immune suppressive medications.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Control group; Former or current smokers without emphysema
Emphysema; Current or former smokers with emphysema

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autoreactive T cell response to elastin fragments	We will examine cytokines released by T cells in response to elastin fragments	One year

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Laura Koth, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: January 11, 2014
• First Submitted That Met QC Criteria: January 11, 2014
• First Posted (Estimate): January 14, 2014

Study Record Updates

• Last Update Posted (Estimate): June 3, 2016
• Last Update Submitted That Met QC Criteria: June 1, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: COPD, chronic obstructive pulmonary disease, emphysema
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases
• Other Study ID Numbers: R01HL110883-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO