Elevated serum levels of the NLRP3 inflammasome are associated with the severity of anti-NMDAR encephalitis in children

Abstract

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis, mainly impacting young females and children. The involvement of the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and related cytokines in pediatric individuals with this condition remains unclear.

Methods: We collected information from 27 children who had anti-NMDAR encephalitis and 12 individuals with non-inflammatory neurological disorders as controls. We used an enzyme-linked immunosorbent assay (ELISA) to identify NLRP3 inflammasome, interleukin (IL)-1β, and IL-18 expression in cerebrospinal fluid (CSF) and matching serum samples. The modified Rankin Scale (mRS) score was performed throughout the acute phase and at the 6-month follow-up to determine the severity of the disease. The area under the curve (AUC) of the receiver operating characteristic curve was utilized to calculate the prediction efficacy.

Results: When compared to controls, individuals with anti-NMDAR encephalitis had significantly increased serum expression of the NLRP3 inflammasome (p < 0.001), IL-1β (p < 0.05), and IL-18 (p < 0.01). In the acute phase, mRS scores were correlated positively with serum levels of NLRP3 inflammasome (p = 0.008), IL-1β (p = 0.023), and IL-18 (p < 0.001). A positive connection was also found between serum levels of NLRP3 inflammasome and IL-1β (p = 0.005). Furthermore, the expression of IL-1β and IL-18 in serum correlated with the 6-month follow-up outcome. The AUC for NLRP3 inflammasome in distinguishing patients with severe neurologic impairments from those with moderate impairments was 0.808 (95 % CI: 0.645-0.972).

Conclusion: In our investigation, children with anti-NMDAR encephalitis have more severe first clinical presentations when their serum concentrations of the NLRP3 inflammasome and related cytokines were higher. These findings provide a potential role for the NLRP3 inflammasome pathway in the pathogenesis of NMDAR encephalitis and provide a basis for targeted therapeutic interventions.

Keywords: Children; Cytokine; NLRP3; anti-NMDAR encephalitis; modified Rankin Scale.