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

Shuwen Deng,Ranran Tu,Ke Qiu,Haiping Zheng,Wei Lu

doi:10.3389/fimmu.2020.609476

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.

Highlights

Acute disseminated encephalomyelitis (ADEM), a postinfectious autoimmune-mediated inflammatory disorder of the central nervous system (CNS), is characterized by widespread demyelination, predominantly involving the white matter of the brain and spinal cord [1]
We investigated the effects of changes at the maternal–fetal interface during pregnancy on the pathogenesis and recurrence of acute disseminated encephalomyelitis (ADEM), as well as the possible role of the high mobility group B1 (HMGB1)/Toll-like receptor 4 (TLR4)/Nf-kB/IL-6 pathway in the pathogenesis of pregnancy-related ADEM
The potential roles of the HMGB1/TLR4/Nf-kB/IL-6 signaling pathway and aquaporin 4 (AQP4) in the pathogenesis of pregnancy-related ADEM were explored by evaluating the relative expression levels of these proteins in the fetal membrane and placenta specimens

Summary

Introduction

Acute disseminated encephalomyelitis (ADEM), a postinfectious autoimmune-mediated inflammatory disorder of the central nervous system (CNS), is characterized by widespread demyelination, predominantly involving the white matter of the brain and spinal cord [1]. The. Pregnancy and Acute Disseminated Encephalomyelitis triggers for immune responses in ADEM are unknown, but the two most widely accepted hypotheses include molecular mimicry and self-sensitization, secondary to CNS infection [2]. Pregnancy and Acute Disseminated Encephalomyelitis triggers for immune responses in ADEM are unknown, but the two most widely accepted hypotheses include molecular mimicry and self-sensitization, secondary to CNS infection [2] These two hypotheses involve complex immune responses, which implicate both T-helper type 1 (Th1) and type 2 (Th2) cytokines, with autoreactive T cells playing a key role in ADEM progression [3,4,5]. It is currently believed that the pathogenesis of ADEM is related to the Th2 cytokine-mediated enhancement of humoral immunity [4]

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Discussion

Conclusion