title: Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma.
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.
authors.affiliation: 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. drerdem@yahoo.com
authors.forename: Erdem
authors.initials: E
authors.lastname: Tüzün
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Joachim M
authors.initials: JM
authors.lastname: Baehring
authors.forename: Serguei
authors.initials: S
authors.lastname: Bannykh
authors.forename: Myrna R
authors.initials: MR
authors.lastname: Rosenfeld
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology*; D004660:Encephalitis / Q000150:complications / Q000276:immunology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000150:complications / Q000276:immunology*; D010257:Paraneoplastic Syndromes; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*; D013724:Teratoma / Q000150:complications / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate
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