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Sarcoidosis resolvers and progressors demonstrate distinct systemic metabolomic profiles
Biorxiv : the Preprint Server for Biology
|March 31, 2025
Summary
Metabolomic analysis reveals distinct metabolic profiles in sarcoidosis patients who progress versus those who resolve. Elevated trimethylamine N-oxide (TMAO) and taurine, with reduced amino acids, indicate metabolic dysfunction in progressive sarcoidosis.
Area of Science:
- Immunology
- Metabolomics
- Systems Biology
Background:
- Sarcoidosis presents with variable clinical outcomes, with immune cell differences previously noted between resolving and progressing disease.
- Programmed Death 1 (PD-1)+Th17 cells are more prevalent in patients with progressive sarcoidosis and idiopathic pulmonary fibrosis (IPF).
- Bioactive metabolites can modulate immune cell function, including Th17 cell proliferation, signaling, and differentiation.
Purpose of the Study:
- To investigate the metabolomic differences between sarcoidosis patients experiencing disease progression versus clinical resolution.
- To identify specific metabolites associated with sarcoidosis clinical outcomes.
Main Methods:
- Metabolomic analysis was performed on serum samples from sarcoidosis patients (n=19) and healthy controls (n=23).
- Sarcoidosis patients were categorized into disease progression or clinical resolution groups prior to treatment.
- Statistical significance for metabolite changes was determined using fold change (>2) and p-value (<0.05) in t-tests, with ANOVA and Tukey's tests for multiple comparisons.
Main Results:
- Progressive sarcoidosis was associated with significantly elevated serum levels of trimethylamine N-oxide (TMAO) and taurine compared to resolving sarcoidosis.
- Patients with progressive sarcoidosis showed significantly reduced concentrations of glycerate, alanine, and proline relative to resolvers.
- Elevated TMAO and taurine, alongside reduced glycerate, alanine, and proline, suggest metabolic pathway disruptions in progressive sarcoidosis.
Conclusions:
- Distinct metabolic profiles correlate with sarcoidosis clinical trajectories.
- Elevated TMAO and taurine, with decreased amino acids, may indicate bioenergetic dysfunction and impaired tissue repair in progressive sarcoidosis.
- These findings highlight the potential role of metabolic alterations in sarcoidosis pathogenesis and progression.
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