Tuzun E, Zhou L, Baehring JM, et al. Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma

Division of Neuro-Oncology, Department of Neurology, Hospital of the University of Pennsylvania, University of Pennsylvania, 3 W. Gates, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Acta Neuropathologica (Impact Factor: 10.76). 09/2009; 118(6):737-43. DOI: 10.1007/s00401-009-0582-4
Source: PubMed

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.

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Available from: Erdem Tüzün, Jul 11, 2014
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    • "However, proportionally, the infrequent immature teratomas have a much higher representation in this condition than the mature cystic ones when compared with their relative overall incidence; mature cystic teratomas are the most frequent ovarian tumors in young females. The higher ratio of immature teratomas associated with this entity can be explained by the large mass of neural tissues present in them which often differentiate neurons and their precursors [13] and that are likely to be related to the formation of Anti NMDAR antibodies [5] [10]. In mature cystic teratomas, neurons are present in only about 7–9% of tumors [14] which often have organoid arrangements reminiscent of central ganglia, cortex and cerebellum [15]. "
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    • "Alternatively, our data showing that the antibodies can activate deposition of both C3b and C5b9 (membrane attack complex) on NMDAR expressing cells would be consistent with direct damage and/or complement-dependent chemotaxis being responsible for a subsequent CSF lymphocytosis. Complement deposition was not found at 3 and 4 months, respectively, in two post-mortem studies (Tuzun et al., 2009) but might be important in the early stages. "
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