Inojosa Hernan, Eisele Judith, Proschmann Undine, Zeissig Sebastian, Akgün Katja, Ziemssen Tjalf
Department of Neurology, Multiple Sclerosis Center, Center of Clinical Neuroscience, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
Department of Medicine I, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
Front Cell Dev Biol. 2020 Sep 25;8:567659. doi: 10.3389/fcell.2020.567659. eCollection 2020.
Fingolimod (FTY) is a sphingosine 1 phosphate (S1P) agonist with significant effects on immune cell distribution used as an effective disease modifying therapy in multiple sclerosis (MS) patients. Animal studies have demonstrated that a dysregulation of egress of murine secretory Immunglobulin A (sIgA)+ plasmablasts from Peyer's patches in FTY-treated mice reduced fecal sIgA levels. Alterations in intestinal levels of sIgA could modify the gut microbiome and homeostasis in humans. We analyzed the effect of FTY on the fecal and salivary sIgA levels as marker of the humoral immune system in the gut.
Twenty five people with confirmed MS diagnosis according to 2010 revised McDonald's criteria and on long-term continuous treatment at the MS Center in Dresden, Germany were enrolled in this exploratory cross-sectional study. Fecal and salivary sIgA were analyzed after at least 12 months of treatment with FTY or Glatiramer acetate (GA).
Fifteen MS patients on FTY and 10 on GA participated in this study. The mean fecal sIgA concentration of both groups was not decreased compared to reference values and did not demonstrate significant differences between them (FTY 3323.13 μg/g +/- 2094.72; GA 2040.65 μg/g +/- 1709.07). A similar pattern was seen in the salivary sIgA and serum immunoglobulins levels.
In this pilot study, we could not confirm the decrease of fecal sIgA after a long-term treatment with FTY. Further longitudinal studies should evaluate the effects of MS treatments on the gut immune system in more detail.
芬戈莫德（FTY）是一种1-磷酸鞘氨醇（S1P）激动剂，对免疫细胞分布有显著影响，在多发性硬化症（MS）患者中用作有效的疾病改善疗法。动物研究表明，在接受FTY治疗的小鼠中，派尔集合淋巴结中鼠分泌型免疫球蛋白A（sIgA）+浆母细胞的流出失调会降低粪便sIgA水平。肠道中sIgA水平的改变可能会改变人类的肠道微生物群和体内平衡。我们分析了FTY对粪便和唾液sIgA水平的影响，将其作为肠道体液免疫系统的标志物。
根据2010年修订的麦克唐纳标准确诊为MS且在德国德累斯顿MS中心接受长期持续治疗的25人纳入了这项探索性横断面研究。在用FTY或醋酸格拉替雷（GA）治疗至少12个月后，分析粪便和唾液sIgA。
15名接受FTY治疗的MS患者和10名接受GA治疗的患者参与了本研究。与参考值相比，两组的平均粪便sIgA浓度均未降低，且两组之间无显著差异（FTY 3323.13μg/g±2094.72；GA 2040.65μg/g±1709.07）。唾液sIgA和血清免疫球蛋白水平也呈现类似模式。
在这项初步研究中，我们无法证实用FTY长期治疗后粪便sIgA会降低。进一步的纵向研究应更详细地评估MS治疗对肠道免疫系统的影响。
