Association of serum Gasdermin D with anti-N-methyl-D-aspartate receptor encephalitis

J Neurochem. 2021 Dec;159(5):923-930. doi: 10.1111/jnc.15497. Epub 2021 Sep 1.

Abstract

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease of the central nervous system. Gasdermin D (GSDMD) is associated with autoimmune disorders and neuroinflammatory disorders, but its role in anti-NMDAR encephalitis is unclear. In this study, we measured serum levels of GSDMD in 42 patients with anti-NMDAR encephalitis and 25 healthy controls. Of the 42 patients, 17 had follow-up evaluation of GSDMD levels and modified Rankin scale (mRS) scores at 3 months. Association of GSDMD with anti-NMDAR encephalitis and its clinical parameters were evaluated. Serum GSDMD levels were significantly higher in patients with anti-NMDAR encephalitis than in healthy controls (p = 0.002, padjusted = 0.009), especially in males (p = 0.001, padjusted = 0.022). This was also evident in patients with severe impairment (mRS >3 vs mRS ≤3; p < 0.001). Serum GSDMD was associated with mRS before and after adjustment for age and gender (r = 0.440 and 0.430, p = 0.004 and 0.006, respectively) as well as serum CH50 (r = -0.419 and -0.426, p = 0.011 and 0.012, respectively). Furthermore, 3-month follow-up evaluation revealed that after treatment, anti-NMDAR encephalitis patients had significantly decreased serum GSDMD levels (p = 0.007) and significantly decreased mRS scores (p = 0.002) compared with before treatment. Furthermore, the changes in mRS scores were negatively associated with changes in GSDMD levels, although the associations were not significant (r = -0.222, p = 0.393). Our findings show that serum GSDMD levels are elevated in anti-NMDAR encephalitis and are associated with disease prognosis.

Keywords: Anti-N-methyl-D-aspartate receptor encephalitis; GSDMD; inflammation; pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / blood*
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / diagnostic imaging*
  • Biomarkers / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Intracellular Signaling Peptides and Proteins / blood*
  • Length of Stay / trends
  • Magnetic Resonance Imaging / methods
  • Male
  • Phosphate-Binding Proteins / blood*
  • Young Adult

Substances

  • Biomarkers
  • GSDMD protein, human
  • Intracellular Signaling Peptides and Proteins
  • Phosphate-Binding Proteins