Higher CSF Levels of NLRP3 Inflammasome Is Associated With Poor Prognosis of Anti-N-methyl-D-Aspartate Receptor Encephalitis

Front Immunol. 2019 May 31:10:905. doi: 10.3389/fimmu.2019.00905. eCollection 2019.

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.

Keywords: NLRP3; anti-NMDAR encephalitis; cytokine; modified Rankin Scale; neuro-inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / cerebrospinal fluid*
  • Cytokines / cerebrospinal fluid
  • Female
  • Humans
  • Inflammasomes / cerebrospinal fluid*
  • Male
  • Middle Aged
  • NLR Family, Pyrin Domain-Containing 3 Protein / cerebrospinal fluid*
  • Prognosis

Substances

  • Cytokines
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human