Development of a Novel Human In Vitro Sarcoidosis Model

There is currently no experimental model that accurately represents sarcoidosis. The lack of a useful research model significantly slows progress towards developing new treatments for sarcoidosis. The investigators plan to develop a new model for sarcoidosis research and will test the model to see if it helps us understand how sarcoidosis develops and if it is useful for testing new treatments.

Study Overview

• Status: Completed
• Conditions: Sarcoidosis
• Intervention / Treatment: Other: No intervention, observational study only

Detailed Description

Sarcoidosis is a systemic granulomatous disease of unknown cause, most commonly affecting the lungs, which tends to afflict young adults in the prime of their lives. Recent data indicating that sarcoidosis mortality rates are rising in the U.S. (1) and Europe (2) highlight the inadequacy of current therapies. As noted in a recent NIH-sponsored sarcoidosis workshop, the lack of relevant animal, computer or in vitro models represents a bottleneck for progress towards understanding disease mechanisms and developing highly effective sarcoidosis treatments (3). The lack of useful disease models likely contributes to the current lack (zero) of investigator-initiated (RO1) projects supporting sarcoidosis research.

The long-term goal of this proposal is to develop a novel human sarcoidosis research model to fill the current void in the field, thereby expediting exploration of basic disease mechanisms and pre-clinical testing of novel therapies. The objective of this application, which is the first step towards achieving the long-term goal, is to develop a novel in vitro human granuloma model to represent abnormal granuloma formation in the context of sarcoidosis. In this regard, a growing body of evidence indicates that mycobacterial antigens are commonly harbored in sarcoidosis tissues, to which these patients are sensitized (4, 5). Our central hypothesis is that the pathological mechanisms of sarcoidosis can be modeled in vitro, as represented by abnormal granuloma formation in response to mycobacterial and other ubiquitous environmental antigens. The feasibility of our proposed model is supported by preliminary studies showing that subjects sensitized to Mycobacterium tuberculosis antigens (latent TB tuberculosis with a positive TB skin test) form well-organized granulomas readily in response to challenge with TB antigens, compared to healthy controls. This project is highly innovative and we feel has an excellent likelihood of leading to a critical breakthrough in the field of sarcoidosis research.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43221
      • Biomedical Research Tower, 10th floor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

primary care clinic

Description

Inclusion Criteria:

• sarcoidosis, subjects (18 - 45 years of age), including 30 sarcoidosis, 15 latent TB and 15 healthy controls.

Exclusion Criteria:

• pregnant women

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Observational study; Blood draw only, observational study	Other: No intervention, observational study only; No intervention. We are collecting blood for an ex vivo study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sarcoidosis patients, volunteers with latent TB, and healthy volunteer subjects will be recruited to donate peripheral blood for isolation of peripheral blood mononuclear cells.	We hypothesize that patients with the active sarcoidosis phenotype will exhibit accelerated granuloma formation with higher IL-10(IL Interleukin)and IL-4 expression relative to patients with the self-limited sarcoidosis phenotype	2-4 years

Collaborators and Investigators

• Sponsor: Elliott Crouser MD
• Investigators: Principal Investigator: Elliott Crouser, MD, Ohio State University

Publications and helpful links

General Publications

• Locke LW, Crouser ED, White P, Julian MW, Caceres EG, Papp AC, Le VT, Sadee W, Schlesinger LS. IL-13-regulated Macrophage Polarization during Granuloma Formation in an In Vitro Human Sarcoidosis Model. Am J Respir Cell Mol Biol. 2019 Jan;60(1):84-95. doi: 10.1165/rcmb.2018-0053OC.
• Crouser ED, White P, Caceres EG, Julian MW, Papp AC, Locke LW, Sadee W, Schlesinger LS. A Novel In Vitro Human Granuloma Model of Sarcoidosis and Latent Tuberculosis Infection. Am J Respir Cell Mol Biol. 2017 Oct;57(4):487-498. doi: 10.1165/rcmb.2016-0321OC.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2012
• Primary Completion (Actual): February 2, 2017
• Study Completion (Actual): February 2, 2017

Study Registration Dates

• First Submitted: May 2, 2013
• First Submitted That Met QC Criteria: May 15, 2013
• First Posted (Estimate): May 20, 2013

Study Record Updates

• Last Update Posted (Actual): November 3, 2021
• Last Update Submitted That Met QC Criteria: November 1, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphoproliferative Disorders; Lymphatic Diseases; Sarcoidosis
• Other Study ID Numbers: 2012H0073