Abstract

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is accepted as an autoimmune disorder of the central nervous system (CNS). NLR family pyrin domain containing 3 (NLRP3) inflammasome, a potent innate inflammatory mediator, can activate IL-1β and induce the migration of T helper cell into CNS. However, the possible role of NLRP3 inflammasome in the pathogenesis of anti-NMDAR encephalitis remains unclear. This study aims to determine the levels of NLRP3 and related cytokines (IL-1β, IL-6, and IL-17) in the cerebrospinal fluid (CSF) of anti-NMDAR encephalitis patients and to assess whether NLRP3 influences the clinical outcomes of this disease. Twenty-five patients with anti-NMDAR encephalitis, 12 viral meningoencephalitis patients and 26 controls with non-inflammatory neurological diseases were recruited. CSF NLRP3 inflammasome, IL-1β, IL-6, and IL-17 were measured by enzyme-linked immunosorbent assay. Thirteen out of 25 patients were re-examed for the concentrations of NLRP3 and cytokines 6 months later. Our results showed significant increases of CSF NLRP3 inflammasome, IL-1β, IL-6, and IL-17 in anti-NMDAR encephalitis patients. There were positive correlations between CSF NLRP3 inflammasome and cytokines in anti-NMDAR encephalitis patients. There was also a positive correlation between maximum modified Rankin Scale (mRS) scores and CSF NLRP3 inflammasome in anti-NMDAR encephalitis patients. During follow-up, the decrease of mRS was positively correlated with the decrease of CSF NLRP3 inflammasomes. These results suggested that the level of CSF NLRP3 inflammasome could represent the severity of anti-NMDAR encephalitis and the reduction of CSF NLRP3 inflammasome could act as an indicator for the prognosis of this disease.

Highlights

  • As an autoimmune disorder, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis predominantly affects young females [1]

  • We detected a significant increase of cerebrospinal fluid (CSF) NLR family pyrin domain containing 3 (NLRP3) inflammasomes and its downstream cytokines in anti-NMDAR encephalitis patients in acute stage, and a decrease in their respective levels during the remission stage

  • Our study revealed the increased CSF NLRP3 inflammasome as an indicator for the severity of anti-NMDAR encephalitis, so the future researches should focus on the attenuating effects of these potential therapeutical drugs in anti-NMDAR encephalitis in vitro or in vivo

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Summary

Introduction

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis predominantly affects young females [1]. Its incidence is approximated at 5–10 per 100,000 people per year [2, 3]. The typical clinical manifestation presents as psychiatric and neurologic symptoms, such as seizures, movements disorders, autonomic dysfunction, and cognition dysfunction [4, 5]. Anti-NMDAR encephalitis may be associated with teratoma and partly secondary to central nervous system (CNS) infections such as herpes simplex virus or parasite [6, 7]. B and T leukocytes have been proposed to be involved in anti-NMDAR encephalitis, the immunopathogenesis of this disease remains obscure. We have reported several inflammatory cytokines were increased in serum or cerebrospinal fluid (CSF) of anti-NMDAR encephalitis [8,9,10]

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