Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma.
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.
Tüzün
Erdem
E
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
Zhou
Lei
L
Baehring
Joachim M
JM
Bannykh
Serguei
S
Rosenfeld
Myrna R
MR
Dalmau
Josep
J
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*
D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate
Acta Neuropathol. 2002 May;103(5):509-15
11935268
Neurology. 2006 Jul 11;67(1):146-9
16832096
Ann Neurol. 2009 Jul;66(1):11-8
19670433
Nat Clin Pract Neurol. 2007 May;3(5):291-6
17479076
Neurology. 2008 Feb 12;70(7):504-11
17898324
Brain. 1999 Jan;122 ( Pt 1):27-39
10050892
Pediatr Radiol. 2005 Jul;35(7):694-7
15723218
Lancet Neurol. 2008 Dec;7(12):1091-8
18851928
Ann Neurol. 2007 Jan;61(1):25-36
17262855
J Neuroimmunol. 2005 Feb;159(1-2):230-7
15652424
J Pathol. 1993 Oct;171(2):83-98
7506771
N Engl J Med. 1990 Jun 28;322(26):1844-51
2348838