Faissner Simon, Bongert Marielena, Trendelenburg Paulina, Thiel Sandra, Yamamura Takashi, Hellwig Kerstin, Gold Ralf
Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, Bochum 44791, Germany.
Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Bochum, Germany.
Ther Adv Neurol Disord. 2024 Feb 16;17:17562864241229321. doi: 10.1177/17562864241229321. eCollection 2024.
Pregnancy in patients with multiple sclerosis (MS) is accompanied by a decline of relapse activity with increased risk of relapses 3 months post-partum, for unknown reasons. Eomesodermin T-helper cells (Eomes Th cells) are known to mediate neuroinflammation and disease progression in MS and are induced by prolactin-secreting cells.
Here, investigated immune cell alterations and the pathophysiological role of Eomes Th cells for disease activity during pregnancy and post-partum in MS.
We enrolled = 81 pregnant patients with relapsing-remitting MS (RRMS), = 27 post-partum RRMS and = 26 female RRMS control patients under the umbrella of the German Multiple Sclerosis and Pregnancy Registry. Clinical data were collected and immune cell alterations were analysed using flow cytometry.
While CD3CD4 Th cells were unaffected, CD3CD8 cytotoxic T-cells were elevated post-partum ( = 0.02) with reduced B-cell frequencies ( = 0.01) compared to non-pregnant RRMS patients. NK cells were elevated during first trimester ( = 0.02) compared to the third trimester. Frequencies of Eomes Th and Eomes Tc cells did not differ. There was no correlation of prolactin release and expression of Eomes Th cells. However, Eomes Th cells correlated with lower frequencies of regulatory T-cells during second ( = -0.42; < 0.05) and third trimester ( = -0.37; < 0.05). Moreover, Eomes Th cells correlated with frequencies of B-cells during third trimester ( = 0.54; = 0.02). Frequencies of Eomes Th cells were not associated with the number of relapses before pregnancy, during pregnancy or post-partum. However, Eomes Th cells strongly correlated with disability post-partum as assessed using the EDSS ( = 0.52; = 0.009).
Pregnancy in MS is associated with robust immunological alterations. Eomes Th cells are capable of inducing immune cell alterations during the course of pregnancy, most evident during the second and third trimester as shown with a correlation of reduced Treg cells and a significant increase of B-cells. Importantly, Eomes Th cells correlate with disability post-partum. In summary, during late pregnancy in MS an inflammatory, cytotoxic and dysregulated immunological environment is primed gaining function post-delivery. This may be responsible for post-partum disability accumulation.
多发性硬化症（MS）患者怀孕时复发活动减少，但产后3个月复发风险增加，原因不明。已知胚外中胚层决定蛋白辅助性T细胞（Eomes Th细胞）介导MS中的神经炎症和疾病进展，且由分泌催乳素的细胞诱导产生。
在此研究MS患者怀孕和产后期间免疫细胞的变化以及Eomes Th细胞对疾病活动的病理生理作用。
在德国多发性硬化症与妊娠登记处的框架下，我们招募了81例复发缓解型MS（RRMS）孕妇、27例RRMS产后患者以及26例RRMS女性对照患者。收集临床数据，并使用流式细胞术分析免疫细胞变化。
与未怀孕的RRMS患者相比，产后CD3CD4 Th细胞未受影响，但CD3CD8细胞毒性T细胞升高（P = 0.02），B细胞频率降低（P = 0.01）。与孕晚期相比，孕早期NK细胞升高（P = 0.02）。Eomes Th细胞和Eomes Tc细胞的频率无差异。催乳素释放与Eomes Th细胞表达无相关性。然而，Eomes Th细胞与孕中期（r = -0.42；P < 0.05）和孕晚期（r = -0.37；P < 0.05）调节性T细胞频率较低相关。此外，Eomes Th细胞与孕晚期B细胞频率相关（r = 0.54；P = 0.02）。Eomes Th细胞频率与怀孕前、怀孕期间或产后的复发次数无关。然而，Eomes Th细胞与产后使用扩展残疾状态量表（EDSS）评估的残疾程度密切相关（r = 0.52；P = 0.009）。
MS患者怀孕与强大的免疫改变有关。Eomes Th细胞能够在怀孕期间诱导免疫细胞变化，在孕中期和孕晚期最为明显，表现为调节性T细胞减少和B细胞显著增加的相关性。重要的是，Eomes Th细胞与产后残疾相关。总之，在MS患者怀孕后期，一种炎症性、细胞毒性和失调的免疫环境在分娩后获得功能。这可能是产后残疾积累的原因。
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