Epigenetic Regulation of Altered T-cell Immunity in Sarcoidosis

Sarcoidosis is a multi-system granulomatous disorder that is triggered and influenced by gene-environment interactions. Although sarcoidosis predominantly affects the lungs in most cases, the clinical disease course is highly variable and any organ can be affected leading to end organ damage despite currently available therapeutics that unfortunately also have numerous and potentially devastating side effects. The environmental triggers of sarcoidosis are unknown but several occupational, environmental and infectious agents have been associated with sarcoidosis in susceptible hosts. Exposure to these triggers result in inflammation, characterized by activation of CD4+ T-cells, cytokine production, subsequent recruitment of other immune cells, and granuloma formation. Although several genetic markers have been associated with sarcoidosis, none fully explain individual susceptibility or clinical course variability, strongly implicating the environment and epigenetics. We have the ability to generate a map of the epigenetic histone modifications in immune cells via Chromatin Immuno-Precipitation coupled with next generation sequencing (ChIP-seq) and a map of transcriptome profiles via RNA-seq. The availability of histone and transcriptional signatures defining T cell activity in sarcoidosis will help identify the specific molecular programs affected by disease processes and can become the basis for future discovery of novel biomarker diagnostics in a clinical setting.

Study Overview

• Status: Recruiting
• Conditions: Sarcoidosis; Sarcoidosis, Pulmonary
• Intervention / Treatment: Other: Observational Study

• Study Type: Observational
• Enrollment (Anticipated): 45

Contacts and Locations

• Study Contact: Name: Victoria Wang, BS; Phone Number: 4154769225; Email: victoria.wang2@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco (Parnassus)
      • Contact: Victoria Wang, BS; Phone Number: 415-476-9225; Email: victoria.wang2@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

People living with Sarcoidosis.

Description

Inclusion Criteria:

• Between the ages of 18 and 85
• Diagnosis of sarcoidosis confirmed by either biopsy or by manifestations consistent with acute sarcoidosis in absence of other known diagnosis.
• Have a suspected diagnosis of sarcoidosis and is scheduled to undergo a biopsy procedure to confirm a diagnosis of sarcoidosis.
• Able to tolerate and willing to undergo study procedures

Exclusion Criteria:

• Current cigarette smoking or smoking within six months prior to the study
• Currently or recently (<6months) on immunosuppressive therapy
• Pregnancy
• Patient inability to participate in the study, such as undergo venipuncture and or BAL

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Controls	Other: Observational Study; Observational study utilizing bronchoscopy, and imaging
Sarcoidosis	Other: Observational Study; Observational study utilizing bronchoscopy, and imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epigenomic Signature of Sarcoidosis	Determine the epigenomic signature of specific histone post-translational modifications associated with CD4+ T cell skewing and activity in sarcoidosis at the site of organ involvement via Chromatin Immuno-Precipitation coupled with next generation sequencing (ChIP-seq) and bronchoalveolar lavage (BAL).	5 years

Collaborators and Investigators

• Sponsor: National Jewish Health
• Collaborators: University of Iowa; University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 5, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): May 6, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Lung Diseases; Lung Diseases, Interstitial; Sarcoidosis, Pulmonary; Sarcoidosis
• Other Study ID Numbers: 15-18171