Shiri-Sverdlov Ronit, Dos Reis Inês Magro, Oligschlaeger Yvonne, Hendrikx Tim, Meesters Dennis M, Vanclooster Annick, Vanhoutvin Nele, Koek Ger H, Westerterp Marit, Binder Christoph J, Cassiman David, Houben Tom
Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6229 ER Maastricht, The Netherlands.
Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
Antioxidants (Basel). 2021 Jan 18;10(1):129. doi: 10.3390/antiox10010129.
As a mediator between lipid metabolism dysfunction, oxidative stress and inflammation, oxidized low-density lipoprotein (oxLDL) is a promising therapeutical target in a wide range of metabolic diseases. In mice, pneumococcal immunization increases anti-phosphorylcholine and oxLDL antibody levels, and reduces atherosclerosis, non-alcoholic steatohepatitis and Niemann-Pick disease burden. These findings suggest that pneumococcal vaccination may be a useful preventive and therapeutical strategy in metabolic disease patients. In this pilot clinical trial, our aim was to determine whether the administration of a pneumococcal vaccine increases anti-phosphorylcholine and anti-oxLDL antibody levels in metabolic disease patients. The following patients were enrolled: four patients with familial partial lipodystrophy (all women, mean age 32 years old); three familial hypercholesterolemia patients (one girl, two boys; mean age 13 years); and two Niemann-Pick type B (NP-B) patients (two men, mean age 37.5 years old). Participants received one active dose of a 13-valent conjugated pneumococcal vaccine (Prevenar 13) and were followed-up for four weeks. Four weeks after Prevenar 13 vaccination, no differences were observed in patients' levels of anti-oxLDL IgM or IgG antibodies. In addition, we observed a reduction in anti-phosphorylcholine (anti-PC) IgM antibody levels, whereas no differences were observed in anti-PC IgG antibody titers. These findings indicate that Prevenar 13 vaccination does not induce an immune response against oxLDL in patients with metabolic diseases. Therefore, Prevenar 13 is not suited to target the metabolic disruptor and pro-inflammatory mediator oxLDL in patients.
作为脂质代谢功能障碍、氧化应激和炎症之间的介质,氧化型低密度脂蛋白(oxLDL)是多种代谢性疾病中一个有前景的治疗靶点。在小鼠中,肺炎球菌免疫可提高抗磷酸胆碱和抗oxLDL抗体水平,并减轻动脉粥样硬化、非酒精性脂肪性肝炎和尼曼-匹克病负担。这些发现表明,肺炎球菌疫苗接种可能是代谢性疾病患者有用的预防和治疗策略。在这项初步临床试验中,我们的目的是确定接种肺炎球菌疫苗是否会提高代谢性疾病患者的抗磷酸胆碱和抗oxLDL抗体水平。纳入了以下患者:4例家族性部分脂肪营养不良患者(均为女性,平均年龄32岁);3例家族性高胆固醇血症患者(1名女孩,2名男孩;平均年龄13岁);以及2例B型尼曼-匹克病(NP-B)患者(2名男性,平均年龄37.5岁)。参与者接种一剂13价结合肺炎球菌疫苗(沛儿13),并随访4周。接种沛儿13疫苗4周后,患者的抗oxLDL IgM或IgG抗体水平未观察到差异。此外,我们观察到抗磷酸胆碱(抗PC)IgM抗体水平降低,而抗PC IgG抗体滴度未观察到差异。这些发现表明,接种沛儿13疫苗不会在代谢性疾病患者中诱导针对oxLDL的免疫反应。因此,沛儿13不适合作为代谢紊乱和促炎介质oxLDL的治疗靶点。