Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients

Simple Summary Multiple sclerosis (MS) is a chronic, inflammatory disease that affects the central nervous system, and is the most common cause of non-traumatic neurological disability in young adults. Although its origin is unknown, it is thought that the immune system damages the insulating covers of nerve cells. On the other hand, it seems that the mitochondria (the organelle producing energy in the cells) function abnormally in these patients. However, few studies focus on the mitochondria of immune cells. In this study, we compared the mitochondrial function of peripheral blood cells (PBC) from healthy donors to those of MS patients, classifying these patients by the presence (M+) or absence (M−) of lipid-specific oligoclonal immunoglobulin M bands (LS-OCMB). The detection of LS-OCMB has been associated with a highly inflammatory and more aggressive course of MS. We found signs of mitochondrial impairment in the PBCs from M+ patients compared with M− ones, which could affect in greater terms the oldest M+ patients. Currently, there is no treatment for this heterogeneous disease. The results of this study could help to understand its physiopathology better and encourage the consideration of the LS-OCMB presence in further studies delving into the effect of certain drugs. Abstract Although impaired mitochondrial function has been proposed as a hallmark of multiple sclerosis (MS) disease, few studies focus on the mitochondria of immune cells. We aimed to compare the mitochondrial function of the peripheral blood mononuclear cells (PBMCs) from MS patients with (M+) and without (M−) lipid-specific oligoclonal immunoglobulin M bands (LS-OCMB), and healthydonors (HD). We conducted an exploratory cross-sectional study with 19 untreated MS patients (M+ = 9 and M− = 10) and 17 HDs. Mitochondrial superoxide anion production and mitochondrial mass in PBMCs were assessed without and with phytohemagglutinin by flow cytometry. The PBMCs’ mitochondrial function was analyzed using Seahorse technology. Superoxide anion production corrected by the mitochondrial mass was higher in MS patients compared with HDs (p = 0.011). Mitochondrial function from M+ patients showed some impairments compared with M− patients. Without stimulus, we observed higher proton leak (p = 0.041) but lower coupling efficiency (p = 0.041) in M+ patients; and under stimulation, lower metabolic potential ECAR (p = 0.011), and lower stressed OCR/ECAR in the same patients. Exclusively among M+ patients, we described a higher mitochondrial dysfunction in the oldest ones. The mitochondrial impairments found in the PBMCs from MS patients, specifically in M+ patients, could help to better understand the disease’s physiopathology.