To report a novel autoimmune encephalitis in which the antibodies target neurexin-3α, a cell adhesion molecule involved in the development and function of synapses.
Five patients with encephalitis and antibodies with a similar pattern of brain reactivity were selected. Antigen precipitation and determination of antibody effects on cultured rat embryonic neurons were performed with reported techniques.
Immunoprecipitation and cell-based assays identified neurexin-3α as the autoantigen of patients' antibodies. All 5 patients (median age 44 years, range 23–50; 4 female) presented with prodromal fever, headache, or gastrointestinal symptoms, followed by confusion, seizures, and decreased level of consciousness. Two developed mild orofacial dyskinesias, 3 needed respiratory support, and 4 had findings suggesting propensity to autoimmunity. CSF was abnormal in all patients (4 pleocytosis, 1 elevated immunoglobulin G [IgG] index), and brain MRI was abnormal in 1 (increased fluid-attenuated inversion recovery/T2 in temporal lobes). All received steroids, 1 IV immunoglobulin, and 1 cyclophosphamide; 3 partially recovered, 1 died of sepsis while recovering, and 1 had a rapid progression to death. At autopsy, edema but no inflammatory cells were identified. Cultures of neurons exposed during days in vitro (div) 7–17 to patients' IgG showed a decrease of neurexin-3α clusters as well as the total number of synapses. No reduction of synapses occurred in mature neurons (div 18) exposed for 48 hours to patients' IgG. Neuronal survival, dendritic morphology, and spine density were unaffected.
an advisory board member for Biogen, and Takeda Pharmaceutical Company Limited
Received funding for travel and/or speaker honoraria from Novartis Pharma, Biogen, Bayer, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical and Astellas Pharma.
Funded as the primary investigator by a JSPS KAKENHI Grant #26461289 (2014-present).
(1) Centro de Estudos Neurologia - Prof. Antonio B.Lefevre, funding for travel to Barcelona for the The Lancet Neurology Autoimmune Disorders Conference for a poster presentation (2) World Congress of Brain, Behavior and Emotion, funding for travel to speak at the conference
Pediatria Catalana, editor advisory board member, since 2010 (this is a local scientific journal and it is not included in Journal Citation Reports released by Thomson Reuters). I don't receive any economical compensation for this.
My salary is funded by the research CM14/00081 grant, from the Instituto Carlos III (Spain).
Research was supported in part by Dodot Procter & Gamble research grant sponsored by Asociaci?n Espa?ola de Pediatr?a (AEP) (DN040579); and Fundaci? Marat? TV3 (20141830).
Patent for Ma2 autoantibody test, patent number: 6,387,639; Issued May 14th, 2002 Patent for NMDA receptor autoantibody test; US 7,972,796 B2 July 5, 2011; European 2057466 Patents filed for GABA(B) receptor autoantibody test, GABA(A) receptor autoantibody test, DPPX autoantibody test, and IgLON5 autoantibody test.
-NIH, RO1NS077851 (previously RO1CA107192), PI, 2011-2016 -NIMH, Eureka 1RO1MH094741, Co-PI, 2011-2015 -Instituto Carlos III, (FIS, 14/00203) -Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya -Fundacio CELLEX
NMDA receptor autoantibody test/Euroimmun GABA(B)R autoantibody test/Euroimmun GABA(A)R autoantibody test/Euroimmun DPPX autoantibody test/Euroimmun Iglon5 autoantibody test/Euroimmun
Patent Ma2 autoantibody test Patent NMDAR autoantibody test Patent application for the use of GABA(B) receptor, GABA (A) receptor, DPPX and IgLON5 autoantiboddy tests
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.