title: Autoimmune encephalitis in humans: how closely does it reflect multiple sclerosis ?
abstract: BACKGROUND
  Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Immunological studies suggest that it is a T-cell mediated autoimmune disease, although an MS-specific target antigen for autoimmunity has so far not been identified. Models of experimental autoimmune encephalomyelitis in part reproduce features of MS, but none of the models so far covers the entire spectrum of pathology and immunology. Autoimmune disease of the nervous system has occasionally been observed in humans after active sensitization with brain tissue or brain cells, giving rise to acute demyelinating polyradiculoneuritis, acute disseminated encephalomyelitis and in rare cases reflecting an inflammatory demyelinating condition similar to acute multiple sclerosis. In this study we analyzed in detail the immunopathology in archival autopsy tissue of a patient who died with an MS like disease after repeated exposure to subcutaneous injections of lyophilized brain cells.
  
  
  RESULTS
  The pathology of this patient fulfilled all pathological diagnostic criteria of MS. Demyelination and tissue injury was associated with antibody (IgM) deposition at active lesion sites and complement activation. Major differences to classical EAE models were seen in the composition of inflammatory infiltrates, being dominated by B-cells, infiltration of IgM positive plasma cells, profound infiltration of the tissue by CD8(+) T-lymphocytes and a nearly complete absence of CD4(+) T-cells.
  
  
  CONCLUSIONS
  Our study shows that auto-sensitization of humans with brain tissue can induce a disease, which closely reflects the pathology of MS, but that the mechanisms leading to demyelination and tissue injury differ from those, generally implicated in the pathophysiology of MS through studies in experimental autoimmune encephalomyelitis.
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Romana
authors.initials: R
authors.lastname: Höftberger
authors.affiliation: Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Marianne
authors.initials: M
authors.lastname: Leisser
authors.affiliation: Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.affiliation: Center for Brain Research, Medical University of Vienna, Vienna, Austria. hans.lassmann@meduniwien.ac.at.
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001344:Autopsy; D001402:B-Lymphocytes / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D004660:Encephalitis / Q000175:diagnosis*; D050031:Hashimoto Disease / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C112986:AIF1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C078341:MYT1 protein, human