Deng Shuwen, Qiu Ke, Tu Ranran, Zheng Haiping, Lu Wei
Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Neurology, The Third Hospital of Changsha, Changsha, China.
Front Immunol. 2021 Feb 1;11:609476. doi: 10.3389/fimmu.2020.609476. eCollection 2020.
The relationship between pregnancy and autoimmune diseases is unclear. This study investigated the possible role of local immune changes and the activation state of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal-fetal interface during pregnancy in the pathogenesis of acute disseminated encephalomyelitis (ADEM). Clinical data and blood samples of a patient with ADEM were collected to observe the dynamic changes in lymphocyte populations after an abortion. The expression of HMGB1, TLR4, Nf-κB, AQP4, IL-2, IL-4, IL-6, and TNF-α in the fetal membrane and placenta was compared between the patient with pregnancy-related ADEM and a woman with a normal pregnancy using Real-time qPCR and western blotting (WB). The patient was diagnosed with ADEM in the early stage of pregnancy after showing limb weakness symptoms. In the third month of gestation, the symptoms worsened, with a disturbance of consciousness and breathing. After the abortion, the patient relapsed with vertigo and visual rotation. Analysis of lymphocyte subsets by flow cytometry showed that B lymphocytes increased, while natural killer T lymphocytes decreased. WB and Real-time qPCR showed that the expression levels of HMGB1, TLR4, Nf-κB, AQP4, and IL-6 in the fetal membrane and placenta were higher in the patient with pregnancy-related ADEM than in the woman with a normal pregnancy, while those of IL-2 were lower in the patient than in the woman with a normal pregnancy. The local immune changes and the activation of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal-fetal interface may be related to the pathogenesis of ADEM.
妊娠与自身免疫性疾病之间的关系尚不清楚。本研究调查了妊娠期间母胎界面处局部免疫变化以及HMGB1/TLR4/Nf-κB/IL-6信号通路的激活状态在急性播散性脑脊髓炎（ADEM）发病机制中的可能作用。收集了一名ADEM患者的临床资料和血液样本，以观察流产后淋巴细胞群体的动态变化。采用实时定量聚合酶链反应（qPCR）和蛋白质免疫印迹法（WB），比较了妊娠相关ADEM患者与正常妊娠女性胎膜和胎盘组织中HMGB1、TLR4、Nf-κB、水通道蛋白4（AQP4）、白细胞介素2（IL-2）、白细胞介素4（IL-4）、白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达。该患者在妊娠早期出现肢体无力症状，被诊断为ADEM。妊娠第三个月时症状加重，出现意识和呼吸障碍。流产后，患者复发眩晕和视物旋转。流式细胞术分析淋巴细胞亚群显示，B淋巴细胞增多，而自然杀伤T淋巴细胞减少。WB和实时定量qPCR结果显示，妊娠相关ADEM患者胎膜和胎盘组织中HMGB1、TLR4、Nf-κB、AQP4和IL-6的表达水平高于正常妊娠女性，而IL-2的表达水平低于正常妊娠女性。母胎界面处的局部免疫变化以及HMGB1/TLR4/Nf-κB/IL-6信号通路的激活可能与ADEM的发病机制有关。
