Archeological neuroimmunology: resurrection of a pathogenic immune response from a historical case sheds light on human autoimmune encephalomyelitis and multiple sclerosis.
Adult
Allergy and Immunology
Animals
Archaeology
Autoimmune Diseases
/ genetics
B-Lymphocytes
/ immunology
Computational Biology
Demyelinating Diseases
/ genetics
Encephalomyelitis
/ genetics
Encephalomyelitis, Autoimmune, Experimental
/ immunology
Female
High-Throughput Nucleotide Sequencing
Humans
Male
Multiple Sclerosis
/ genetics
Myelin-Oligodendrocyte Glycoprotein
/ genetics
Neurology
Paraffin Embedding
RNA, Messenger
/ biosynthesis
Rats
Tissue Fixation
Transcriptome
Human autoimmune encephalitis
Multiple sclerosis (MS)
Myelin oligodendrocytes glycoprotein
Next generation sequencing
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
24
09
2020
accepted:
13
10
2020
revised:
07
10
2020
pubmed:
27
11
2020
medline:
26
10
2021
entrez:
26
11
2020
Statut:
ppublish
Résumé
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).
Identifiants
pubmed: 33242149
doi: 10.1007/s00401-020-02239-2
pii: 10.1007/s00401-020-02239-2
pmc: PMC7785560
doi:
Substances chimiques
MOG protein, human
0
Myelin-Oligodendrocyte Glycoprotein
0
RNA, Messenger
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
67-83Subventions
Organisme : Austrian Science Fund FWF
ID : I 3334
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : I 3335
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : I 4685
Pays : Austria
Commentaires et corrections
Type : ErratumIn
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