Archeological neuroimmunology: resurrection of a pathogenic immune response from a historical case sheds light on human
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ORIGINAL PAPER
Archeological neuroimmunology: resurrection of a pathogenic immune response from a historical case sheds light on human autoimmune encephalomyelitis and multiple sclerosis Eduardo Beltrán1 · Manuela Paunovic2 · David Gebert1 · Emine Cesur2 · Markus Jeitler3 · Romana Höftberger4 · Joachim Malotka1 · Simone Mader1 · Naoto Kawakami1 · Edgar Meinl1 · Monika Bradl2 · Klaus Dornmair1,5 · Hans Lassmann2 Received: 24 September 2020 / Revised: 7 October 2020 / Accepted: 13 October 2020 © The Author(s) 2020
Abstract Aim of our study was to identify the target auto-antigen in the central nervous system recognized by the immune system of a unique patient, who died more than 60 years ago from a disease with pathological changes closely resembling multiple sclerosis (MS), following a misguided immunization with lyophilized calf brain tissue. Total mRNA was isolated from formaldehyde fixed and paraffin embedded archival brain tissue containing chronic active inflammatory demyelinating lesions with inflammatory infiltrates rich in B-lymphocytes and plasma cells. Analysis of the transcriptome by next generation sequencing and reconstruction of the dominant antibody by bioinformatic tools revealed the presence of one strongly expanded B-cell clone, producing an autoantibody against a conformational epitope of myelin oligodendrocytes glycoprotein (MOG), similar to that recognized by the well characterized monoclonal anti-MOG antibody 8-18C5. The reconstructed antibody induced demyelination after systemic or intrathecal injection into animals with T-cell mediated encephalomyelitis. Our study suggests that immunization with bovine brain tissue in humans may—in a small subset of patients—induce a disease with an intermediate clinical and pathological presentation between MS and MOG-antibody associated inflammatory demyelinating disease (MOGAD). Keywords Next generation sequencing · Myelin oligodendrocytes glycoprotein · Multiple sclerosis (MS) · Human autoimmune encephalitis
Introduction Multiple sclerosis is seen as an autoimmune disease, although so far no MS-specific pathogenic autoimmune reaction has been identified [15, 16]. Despite this caveat, Eduardo Beltrán and Manuela Paunovic contributed equally to this work. Monika Bradl, Klaus Dornmair and Hans Lassmann shared senior authorship. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00401-020-02239-2) contains supplementary material, which is available to authorized users. * Hans Lassmann [email protected] Extended author information available on the last page of the article
experimental autoimmune encephalomyelitis (EAE) in various different animal species serves as a key disease model for MS [11, 25]. Long before the first accounts of EAE in experimental animals [39, 44] it was already known from experience with rabies vaccination that active sensitization of humans with brain tissue can trigger a demyelinating encephalomyelitis [2, 21]. Formal proof for the autoimmune nature of this condition w
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