多发性硬化症(MS)急性复发的主要治疗方法是静脉内施用高剂量甲基强的松龙(IVMP)。然而,皮质类固醇治疗对MS(pwMS)患者急性神经炎症的影响机制尚不完全清楚.特别是,迄今为止,糖皮质激素(GC)对先天免疫系统细胞的诱导变化以及不同免疫疗法患者之间的差异很少受到关注.
■我们使用流式细胞术对复发期间接受IVMP治疗的pwMS的外周血单核细胞进行了免疫表型分型。我们比较了IVMP治疗对三组中多种免疫细胞亚群的影响:12名患者未接受疾病修饰治疗(wDMT),10名患者接受平台治疗(PT),18名患者接受芬戈莫德治疗(FTY)。
■我们观察到IVMP对不同免疫细胞亚群的显著的个体间短期和中期效应。除了有据可查的T辅助细胞(Th细胞)减少外,我们在首次输注IVMP后检测到中性粒细胞的先天性免疫反应中的显著改变,嗜酸性粒细胞和嗜碱性粒细胞,单核细胞和浆细胞样树突状细胞(pDC)。在将患者wDMT与PT和FTY队列进行比较时,我们发现,在所有治疗组中,IVMP对先天免疫细胞的影响相似.然而,在FTY治疗下,我们未观察到已有淋巴细胞减少的患者在IVMP期间T淋巴细胞计数进一步显著下降.尽管T细胞凋亡被认为是GCs的主要作用机制,FTY患者在IVMP治疗后仍报告症状改善.
■除了T细胞抑制,我们的数据表明GC的进一步免疫调节机制,特别是对先天免疫反应的细胞,比以前理解的意义更大。由于DMT对适应性免疫细胞的调节,GC对这些细胞的影响取决于潜在的DMT。涉及较大队列和脑脊液样本的其他研究是必要的,以更深入地了解在复发期间具有不同DMT的pwMS中对GC的免疫反应,以定义和解释临床反应谱的差异。
UNASSIGNED: The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date.
UNASSIGNED: We conducted immunophenotyping using flow cytometry on peripheral blood mononuclear cells of pwMS who received IVMP treatment during a relapse. We compared the impact of an IVMP treatment on a broad variety of immune cell subsets within three groups: twelve patients who were treatment-naïve to disease modifying therapies (wDMT) to ten patients on platform therapies (PT) and eighteen patients on fingolimod therapy (FTY).
UNASSIGNED: We observed pronounced interindividual short- and intermediate-term effects of IVMP on distinct immune cells subsets. In addition to the well-documented decrease in T-helper cells (Th cells), we detected significant alterations after the first IVMP infusion within the innate immune response among neutrophil, eosinophil and basophil granulocytes, monocytes and plasmacytoid dendritic cells (pDCs). When comparing patients wDMT to the PT and FTY cohorts, we found that IVMP had a similar impact on innate immune cells across all treatment groups. However, we did not observe a significant further decline in T lymphocyte counts during IVMP in patients with pre-existing lymphopenia under FTY treatment. Although T cell apoptosis is considered the main mechanism of action of GCs, patients with FTY still reported symptom improvement following IVMP treatment.
UNASSIGNED: In addition to T cell suppression, our data suggests that further immunoregulatory mechanisms of GC, particularly on cells of the innate immune response, are of greater significance than previously understood. Due to the regulation of the adaptive immune cells by DMTs, the impact of GC on these cells varies depending on the underlying DMT. Additional studies involving larger cohorts and cerebrospinal fluid samples are necessary to gain a deeper understanding of the immune response to GC in pwMS with different DMTs during relapse to define and explain differences in clinical response profiles.