# Precision Medicine in Sarcoidosis

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $914,660

## Abstract

ABSTRACT
Sarcoidosis is a systemic inflammatory disease of unknown etiology characterized by non-caseating
granulomas in affected organs, primarily in the lungs. Approximately 30% of patients with sarcoidosis progress
to debilitating disease; however, the drivers of susceptibility or resilience to disease remain poorly understood.
An inflammatory response to an undefined antigen is postulated as the etiology of granuloma formation, and
the pathogenesis has been suggested to involve gene-pathogen interaction, yet analysis of single genes or
microbes has not proven applicable to diagnosis of all forms of sarcoidosis. Indeed, rather than a single
organism, the disease may represent an interaction between the community of organisms that comprise the
lung microbiome (community of organisms that live in and on us) and the host immune response. We propose
that understanding the microbiome/host interaction will suggest strategies for precision medicine approaches
to sarcoidosis. This proposal addresses this significant gap by investigating interactions between the lung
microbiome, host immune and clinical responses in sarcoidosis using multiomics approaches – a critically
innovative strategy. Our preliminary data support our novel hypotheses. First, we identified distinct lung
microbiomes that differentiated patients with sarcoidosis versus controls. Second, our results identified
biomarkers of disease severity that were associated with decreased lung function. Third, a recurrent analytic
theme that emerged, regardless of the type of -omic analysis, was that sarcoidosis is characterized by
pathways related to apoptosis and autophagy, which is consistent with our observation of decreased
abundance of peripheral lymphocytes and functional immune anergy. These data led us to our Overall
Hypothesis: Lung microbiome and host immune interactions characterized by apoptosis and autophagy
pathways influence sarcoidosis clinical course. This hypothesis will be tested by an observational prospective
and validation study of sarcoidosis patients at 5 time points to facilitate time series analyses. Aims 1 and 2
focus on lung microbiome or host immune responses, respectively, in relation to clinical course of sarcoidosis.
Using these data in Aim 3, predictive models will be constructed based on integrated data of metagenomic and
host-immune interactions. The novelty and significance of our multiomics strategy is to construct models for
precision medicine therapies to harness bioinformatic strategies into focused, patient-specific approaches. The
long-term significance of this study is to define pathways for sarcoidosis progression or resolution, and to
develop database of these findings to further develop more precise, testable, models.

## Key facts

- **NIH application ID:** 9851921
- **Project number:** 5R01HL138628-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Patricia W Finn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $914,660
- **Award type:** 5
- **Project period:** 2018-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851921

## Citation

> US National Institutes of Health, RePORTER application 9851921, Precision Medicine in Sarcoidosis (5R01HL138628-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851921. Licensed CC0.

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