Domínguez-Mozo María Inmaculada, García-Frontini Nieto María Celeste, Gómez-Calcerrada María Isabel, Pérez-Pérez Silvia, García-Martínez María Ángel, Villar Luisa María, Villarrubia Noelia, Costa-Frossard Lucienne, Arroyo Rafael, Alvarez-Lafuente Roberto
Environmental Factors in Degenerative Diseases Research Group, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain.
Department of Immunology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28040 Madrid, Spain.
Biology (Basel). 2022 Nov 8;11(11):1633. doi: 10.3390/biology11111633.
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 ( = 0.011). Mitochondrial function from M+ patients showed some impairments compared with M- patients. Without stimulus, we observed higher proton leak ( = 0.041) but lower coupling efficiency ( = 0.041) in M+ patients; and under stimulation, lower metabolic potential ECAR ( = 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.
尽管线粒体功能受损被认为是多发性硬化症（MS）的一个标志，但很少有研究关注免疫细胞的线粒体。我们旨在比较来自伴有（M+）和不伴有（M-）脂质特异性寡克隆免疫球蛋白M带（LS-OCMB）的MS患者以及健康供体（HD）的外周血单个核细胞（PBMC）的线粒体功能。我们对19例未经治疗的MS患者（M+ = 9例，M- = 10例）和17名HD进行了一项探索性横断面研究。通过流式细胞术在有无植物血凝素的情况下评估PBMC中的线粒体超氧阴离子产生和线粒体质量。使用海马技术分析PBMC的线粒体功能。与HD相比，MS患者中经线粒体质量校正的超氧阴离子产生更高（P = 0.011）。与M-患者相比，M+患者的线粒体功能存在一些损害。在无刺激情况下，我们观察到M+患者有更高的质子泄漏（P = 0.041）但耦合效率更低（P = 0.041）；在刺激情况下，同一患者的代谢潜能胞外酸化率（ECAR）更低（P = 0.011），且应激状态下的氧耗率/ECAR更低。仅在M+患者中，我们发现年龄最大的患者线粒体功能障碍更严重。在MS患者的PBMC中发现的线粒体损害，特别是在M+患者中，可能有助于更好地理解该疾病的病理生理学。
