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Acta Neuropathologica

, 118:737 | Cite as

Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma

  • Erdem TüzünEmail author
  • Lei Zhou
  • Joachim M. Baehring
  • Serguei Bannykh
  • Myrna R. Rosenfeld
  • Josep Dalmau
Original Paper

Abstract

We report the immunopathological analysis of the brain and tumor of two patients who died of anti-NMDAR-associated encephalitis, and of the tumor of nine patients who recovered. Findings included prominent microgliosis and deposits of IgG with rare inflammatory infiltrates in the hippocampus, forebrain, basal ganglia, and spinal cord. Detection of cells expressing markers of cytotoxicity (TIA, granzyme B, perforin and Fas/Fas ligand) was extremely uncommon. All tumors showed NMDAR-expressing neurons and inflammatory infiltrates. All patients’ NMDAR antibodies were IgG1, IgG2, or IgG3. No complement deposits were observed in any of the central nervous system regions examined. Overall, these findings coupled with recently reported in vitro data showing that antibodies downregulate the levels of NMDA receptors suggest that the antibody immune-response is more relevant than cytotoxic T-cell mechanisms in the pathogenesis of anti-NMDAR-associated encephalitis.

Keywords

Paraneoplastic Limbic encephalitis NMDA Antibodies Teratoma 

Notes

Acknowledgment

This work was supported in part by RO1CA89054, RO1CA107192 (JD).

Supplementary material

401_2009_582_MOESM1_ESM.jpg (374 kb)
Supplementary Figure 1. Inflammatory infiltrates in the control tumor sample. Panels a–f, control tumor sections immunolabeled for the presence of CD8+ cells (a), granzyme-b (b), perforin (c), Fas (d), Fas ligand (e) and TIA-1 (f). All panels original magnification ×400, avidin–biotin–peroxidase technique with mild hematoxylin counterstaining. All studies were performed with paraffin-embedded sections (JPG 374 kb)

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Erdem Tüzün
    • 1
    Email author
  • Lei Zhou
    • 1
  • Joachim M. Baehring
    • 2
  • Serguei Bannykh
    • 2
  • Myrna R. Rosenfeld
    • 1
  • Josep Dalmau
    • 1
  1. 1.Division of Neuro-Oncology, Department of NeurologyHospital of the University of Pennsylvania, University of PennsylvaniaPhiladelphiaUSA
  2. 2.Yale University School of MedicineNew HavenUSA

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