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Low frequency of N-methyl-D-aspartate receptor autoimmunity in tick-borne encephalitis

Jakob Morén1,2, Barbro Persson3, Anna Sörman3

  • 1Infection Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Plos One
|October 13, 2025
PubMed
Abstract

Insights

Autoantibodies against the N-methyl-D-aspartate receptor (anti-NMDAR) rarely develop after tick-borne encephalitis. Further research is needed to understand their role in cognitive issues in some patients.

Area of Science:

  • Neuroimmunology
  • Infectious Diseases
  • Neurology

Background:

  • Tick-borne encephalitis (TBE) is a central nervous system viral infection with poorly understood mechanisms and potential long-term effects.
  • Autoimmune encephalitis, characterized by autoantibodies against the N-methyl-D-aspartate receptor (anti-NMDAR), can be triggered by various events and may complicate recovery from other encephalitides.
  • While TBE has been anecdotally linked to anti-NMDAR encephalitis, the frequency of this autoimmunization is unknown.

Purpose of the Study:

  • To determine the frequency of intrathecal anti-NMDAR antibody development post-TBE.
  • To investigate the potential association between anti-NMDAR antibodies and cognitive complaints in TBE patients.

Main Methods:

  • Retrospective and prospective analysis of adult patients diagnosed with TBE.
  • Detection of anti-NMDAR IgG antibodies in cerebrospinal fluid (CSF) using two commercial kits.
  • Analysis of 71 CSF samples from 53 patients, collected a median of 91 days post-symptom onset.

Main Results:

  • Anti-NMDAR antibodies were detected in CSF samples from one TBE patient.
  • This represents an incidence of 1.9% (95% CI: 0.05-10.1%) of the studied TBE patient cohort.
  • The positive samples were identified using Euroimmun AG kits.

Conclusions:

  • Intrathecal anti-NMDAR autoantibody development following TBE is infrequent.
  • The clinical significance of these antibodies for cognitive outcomes in a subset of patients requires further investigation.
  • Consideration of anti-NMDAR antibody testing in CSF may be warranted for TBE patients experiencing post-recovery clinical decline.

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