Smoking Tobacco Increases Extracellular Vesicles and Alters Their Cargo in the Blood of Multiple Sclerosis Patients 9219

Abstract Description Multiple sclerosis (MS) is a chronic disease of the central nervous system that is characterized by a widely variable prognosis. While some patients experience a relatively mild course, others suffer from severe disease progression. Tobacco smoke is an environmental factor known to worsen MS outcomes; however, the mechanism by which it exerts its detrimental effects is unclear. Here, we used the OLINK-Explore assay to profile 1,466 serum proteins in MS patients who were smokers or non-smokers, as well as in healthy controls. Smoking significantly increased levels of proteins associated with the extracellular vesicle (EV) cellular compartment, an effect more pronounced in patients compared to healthy individuals. Ultracentrifugation isolation of EVs confirmed that MS smokers had significantly more plasma exosomes (30–150 nm vesicles) compared to non-smoker patients and healthy non-smokers. Mass-spectrometry of exosomes revealed 20 differentially abundant proteins, including elevated SerpinA1 in non-smokers and Trim33 in smokers. In vitro experiments showed that cigarette smoke extract (CSE) directly induced EV release from immune cells, including T cells, B cells, and monocytes. These findings suggest that tobacco smoke drives the release of EVs, potentially exacerbating immune cell dysfunction in MS. Our ongoing research aims to further characterize the cargo and functional differences of EVs in smoker and non-smoker patients to better understand their role in disease. Funding Sources presbyterian health foundation Topic Categories Neuroimmunology (NEUR)