Peripheral Mononuclear Cells Metabolomics in Obstructive Sleep Apnea Syndrome (OSAS): An Exploratory Pilot Study of Immunometabolic Signatures

Obstructive Sleep Apnea Syndrome (OSAS) is associated with systemic inflammation and immune dysfunction, yet the specific metabolic alterations within immune cells remain poorly understood. In this exploratory study, we characterized the metabolome of peripheral mononuclear cells (PMNCs) from patients with OSAS and healthy controls to investigate potential immunometabolic signatures associated with the disease. Initial analyses identified 21 nominally differentially abundant metabolites between OSAS patients and controls, suggesting trends such as the depletion of carnitines and alterations in fatty acid and neurotransmitter metabolism. However, following correction for multiple testing (False Discovery Rate, FDR), only putatively annotated cis,cis-muconic acid remained statistically significant. Furthermore, pathway enrichment analysis highlighted exploratory trends primarily associated with SLC-mediated transmembrane transport and energy metabolism. Our findings indicate that while OSAS PMNCs exhibit metabolic shifts suggestive of cellular stress, most of these alterations represent nominal trends that require validation in larger cohorts. The robust identification of putatively annotated cis,cis-muconic acid highlights a potential target of interest. In this exploratory pilot study, given the absence of polysomnographic and objective hypoxia parameters in most participants, observed metabolic alterations are described as associated with, rather than directly caused by, intermittent hypoxia. Overall, this study provides a hypothesis-generating framework for future research on the immunometabolic consequences of OSAS.