Intrathecal Antibody Production Against Epstein-Barr, Herpes Simplex, and Other Neurotropic Viruses in Autoimmune Encephalitis.

Neurol Neuroimmunol Neuroinflamm

From the Department of Neurology (P.S., T.S., F.F.K., Nora Möhn, M.S., K.-W.S.), Hannover Medical School; Department of Neurology (P.L.), Georg August University Göttingen; Department of Neurology (M.D., J.L.), Ulm University; Department of Neurology (M.R.), Medical Faculty, Heinrich-Heine-University Düsseldorf; Department of Neurology (M.R., T.M.), Centre for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf; Institute of Neuroimmunology and Multiple Sclerosis (M.A.F.), University Medical Center Hamburg-Eppendorf; Department of Neurology with Institute of Translational Neurology (Nico Melzer), University Hospital Muenster; Department of Neurology (M.P.M.), University Hospital Cologne; Division of Neuropediatrics and Social Pediatrics (M.H.), Department of Pediatrics, Medical Faculty, RWTH Aachen University; and Institute of Clinical Neuroimmunology (F.S.T.), University Hospital and Biomedical Center, Ludwig-Maximilians University Munich, Germany.

Published: November 2021

Background And Objectives: Neurotropic viruses are suspected to play a role in the pathogenesis of autoimmune diseases of the CNS such as the association between the Epstein-Barr virus (EBV) and multiple sclerosis (MS). A group of autoimmune encephalitis (AE) is linked to antibodies against neuronal cell surface proteins. Because CNS infection with the herpes simplex virus can trigger anti-NMDA receptor (NMDAR) encephalitis, a similar mechanism for EBV and other neurotropic viruses could be postulated. To investigate for previous viral infections of the CNS, intrathecally produced virus-specific antibody synthesis was determined in patients with AE.

Methods: Antibody-specific indices (AIs) against EBV and measles, rubella, varicella zoster, herpes simplex virus, and cytomegalovirus were determined in 27 patients having AE (anti-NMDAR encephalitis, n = 21, and LGI1 encephalitis, n = 6) and in 2 control groups comprising of 30 patients with MS and 21 patients with noninflammatory CNS diseases (NIND), which were sex and age matched.

Results: An intrathecal synthesis of antibodies against EBV was found in 5/27 (19%) patients with AE and 2/30 (7%) of the patients with MS. All these patients had also at least 1 additional elevated virus-specific AI. In contrast, in none of the patients with NIND, an elevated virus-specific AI was detected.

Discussion: Intrathecally produced antibodies against EBV can be found in patients with AE and MS but only together with antibodies against different neurotropic viruses. Evidence of these antibodies is the result of a polyspecific immune response similar yet distinct from MS response rather than an elapsed infection of the CNS.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387013PMC
http://dx.doi.org/10.1212/NXI.0000000000001062DOI Listing

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