Relationship Between Pregnancy and Acute Disseminated Encephalomyelitis: A Single-Case Study

Abstract

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.

Pregnancy-Related Attack in Neuromyelitis Optica Spectrum Disorder With AQP4-IgG: A Single-Center Study and Meta-Analysis

“…AQP4 is expressed in the human placenta during gestation and plays a regulatory role in the maternal–fetal fluid exchange between placental cells and fetal capillaries in healthy mothers ( 32 , 33 ). We found increased levels of AQP4 in the placenta and fetal membrane in a patient with acute disseminated encephalomyelitis onset in pregnancy as compared to that in a healthy control; this may be due to the activation of the HMGB1/TLR4/Nf-kB/IL-6 pathway ( 34 ). Therefore, we speculate that the increased levels of AQP4 on the placenta were mistakenly identified as “foreign proteins” due to the alteration of the immunological state during pregnancy, leading to the occurrence of autoimmune reactions and stimulating production of AQP4-ab in the serum.…”

An Adult Case of Adenovirus-Associated Acute Disseminated Encephalomyelitis

“…ADEM is a rare immune mediated demyelinating disorder of the CNS that is most widely thought to be a post-infectious and post-vaccination autoimmune phenomenon [ 10 ]. The etiology of ADEM is still poorly understood, but there are two proposed mechanisms [ 11 ]. The first theory is molecular mimicry.…”

AQP2 Promotes Astrocyte Activation by Modulating the TLR4/NFκB-p65 Pathway Following Intracerebral Hemorrhage

“…AQP4 is the most studied AQP in the CNS and is mainly distributed in astrocytes. AQP4 contributes to the development of inflammatory demyelination diseases of the CNS (neuromyelitis optica spectrum disorder [NMOSD] or acute disseminated encephalomyelitis [ADEM]) ( 24 ) and promotes brain inflammation in neurodegenerative diseases ( 25 ), stroke ( 26 ), and other disorders ( 27 ). AQP4 is also involved in astrocyte-microglia communication when water passes through the lamellipodium and into the cytoplasm via an osmotic gradient ( 28 , 29 ).…”