The peripheral network between oxidative stress and inflammation in multiple sclerosis

Reactive oxygen species (ROS) are mainly produced by microglia and macrophages during inflammation-driven oxidative burst. However, they can in turn affect the reactivity and function of immune cells. For the first time, the relationship between these two key players involved in Multiple Sclerosis (MS) was evaluated at peripheral level. We performed an in-depth immune-phenotypic and functional analysis of MBP (Myelin Basic Protein)-stimulated Peripheral Blood Mononuclear Cells (PBMCs) by flow-cytometry. In addition, blood Coenzyme-Q10 (CoQ10), total, oxidized and reduced forms of glutathione (GSTot, GSSG, GSH), malondialdehyde (MDA), ROS, anti-oxidized-low-density-lipoproteins antibodies (anti-oxLDL), and anti-oxidant-power (PAO) were studied in 31 untreated MS patients (MSnoTP), 23 MS patients (MSTP) treated with Disease Modifying Drugs (DMDs) and 39 matched controls (HC). The focus of our study was the correlation between oxidative stress biomarkers and distribution of immune-phenotypes across the 3 studied groups. In MSnoTP an inverse correlation between MDA and apoptotic cells (CD4+ AnnexinV+ TIM3+) was detected (rs=-0.50, p=0.01). Ml functional phenotype (CD14+IL6+) and TH17 cells (CD4+ IL22+) inversely (rs=-0.48) and directly (rs=0.46) correlated (p = 0.01) with Anti-oxLDL antibodies and GSSG, respectively. The latter direct correlation was shown also in MSTP. Notably, in this group, we also detected a direct correlation between CD4+ IL4+ and CD4+ IL25+ (TH2 phenotype) with CoQ10 (rs=0.54) and GSH (rs=0.46) (p