Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS

  1. Gerhards, Ramona ORCID logo
  2. Pfeffer, Lena Kristina
  3. Lorenz, Jessica
  4. Starost, Laura
  5. Nowack, Luise
  6. Thaler, Franziska S.
  7. Schlüter, Miriam
  8. Rübsamen, Heike
  9. Macrini, Caterina
  10. Winklmeier, Stephan
  11. Mader, Simone
  12. Bronge, Mattias
  13. Grönlund, Hans
  14. Feederle, Regina
  15. Hsia, Hung-En
  16. Lichtenthaler, Stefan F.
  17. Merl-Pham, Juliane
  18. Hauck, Stefanie M.
  19. Kuhlmann, Tanja
  20. Bauer, Isabel J.
  21. Beltran, Eduardo
  22. Gerdes, Lisa Ann
  23. Mezydlo, Aleksandra
  24. Bar-Or, Amit
  25. Banwell, Brenda
  26. Khademi, Mohsen
  27. Olsson, Tomas
  28. Hohlfeld, Reinhard
  29. Lassmann, Hans
  30. Kümpfel, Tania
  31. Kawakami, Naoto
  32. Meinl, Edgar ORCID logo

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1000 Titel
  • Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS
1000 Autor/in
  1. Gerhards, Ramona |
  2. Pfeffer, Lena Kristina |
  3. Lorenz, Jessica |
  4. Starost, Laura |
  5. Nowack, Luise |
  6. Thaler, Franziska S. |
  7. Schlüter, Miriam |
  8. Rübsamen, Heike |
  9. Macrini, Caterina |
  10. Winklmeier, Stephan |
  11. Mader, Simone |
  12. Bronge, Mattias |
  13. Grönlund, Hans |
  14. Feederle, Regina |
  15. Hsia, Hung-En |
  16. Lichtenthaler, Stefan F. |
  17. Merl-Pham, Juliane |
  18. Hauck, Stefanie M. |
  19. Kuhlmann, Tanja |
  20. Bauer, Isabel J. |
  21. Beltran, Eduardo |
  22. Gerdes, Lisa Ann |
  23. Mezydlo, Aleksandra |
  24. Bar-Or, Amit |
  25. Banwell, Brenda |
  26. Khademi, Mohsen |
  27. Olsson, Tomas |
  28. Hohlfeld, Reinhard |
  29. Lassmann, Hans |
  30. Kümpfel, Tania |
  31. Kawakami, Naoto |
  32. Meinl, Edgar |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-11-30
1000 Erschienen in
1000 Quellenangabe
  • 8(1):207
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s40478-020-01086-2 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706210/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Autoimmune disorders of the central nervous system (CNS) comprise a broad spectrum of clinical entities. The stratification of patients based on the recognized autoantigen is of great importance for therapy optimization and for concepts of pathogenicity, but for most of these patients, the actual target of their autoimmune response is unknown. Here we investigated oligodendrocyte myelin glycoprotein (OMGP) as autoimmune target, because OMGP is expressed specifically in the CNS and there on oligodendrocytes and neurons. Using a stringent cell-based assay, we detected autoantibodies to OMGP in serum of 8/352 patients with multiple sclerosis, 1/28 children with acute disseminated encephalomyelitis and unexpectedly, also in one patient with psychosis, but in none of 114 healthy controls. Since OMGP is GPI-anchored, we validated its recognition also in GPI-anchored form. The autoantibodies to OMGP were largely IgG1 with a contribution of IgG4, indicating cognate T cell help. We found high levels of soluble OMGP in human spinal fluid, presumably due to shedding of the GPI-linked OMGP. Analyzing the pathogenic relevance of autoimmunity to OMGP in an animal model, we found that OMGP-specific T cells induce a novel type of experimental autoimmune encephalomyelitis dominated by meningitis above the cortical convexities. This unusual localization may be directed by intrathecal uptake and presentation of OMGP by meningeal phagocytes. Together, OMGP-directed autoimmunity provides a new element of heterogeneity, helping to improve the stratification of patients for diagnostic and therapeutic purposes.
1000 Sacherschließung
lokal Neuroinflammation
lokal Encephalomyelitis, Acute Disseminated/immunology [MeSH]
lokal Autoantibodies/immunology [MeSH]
lokal Autoimmunity
lokal Male [MeSH]
lokal Multiple Sclerosis/immunology [MeSH]
lokal Case-Control Studies [MeSH]
lokal Child [MeSH]
lokal Disease Models, Animal [MeSH]
lokal Autoantigen
lokal Female [MeSH]
lokal Oligodendrocyte-Myelin Glycoprotein/immunology [MeSH]
lokal T-Lymphocytes/immunology [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Rats [MeSH]
lokal Middle Aged [MeSH]
lokal Encephalomyelitis, Autoimmune, Experimental/immunology [MeSH]
lokal Animals [MeSH]
lokal Immunoglobulin G/immunology [MeSH]
lokal Autoimmunity/immunology [MeSH]
lokal Mice [MeSH]
lokal Multiple sclerosis
lokal Psychotic Disorders/immunology [MeSH]
lokal Research
lokal Young Adult [MeSH]
lokal Child, Preschool [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-5398-3632|https://frl.publisso.de/adhoc/uri/UGZlZmZlciwgTGVuYSBLcmlzdGluYQ==|https://frl.publisso.de/adhoc/uri/TG9yZW56LCBKZXNzaWNh|https://frl.publisso.de/adhoc/uri/U3Rhcm9zdCwgTGF1cmE=|https://frl.publisso.de/adhoc/uri/Tm93YWNrLCBMdWlzZQ==|https://frl.publisso.de/adhoc/uri/VGhhbGVyLCBGcmFuemlza2EgUy4=|https://frl.publisso.de/adhoc/uri/U2NobMO8dGVyLCBNaXJpYW0=|https://frl.publisso.de/adhoc/uri/UsO8YnNhbWVuLCBIZWlrZQ==|https://frl.publisso.de/adhoc/uri/TWFjcmluaSwgQ2F0ZXJpbmE=|https://frl.publisso.de/adhoc/uri/V2lua2xtZWllciwgU3RlcGhhbg==|https://frl.publisso.de/adhoc/uri/TWFkZXIsIFNpbW9uZQ==|https://frl.publisso.de/adhoc/uri/QnJvbmdlLCBNYXR0aWFz|https://frl.publisso.de/adhoc/uri/R3LDtm5sdW5kLCBIYW5z|https://frl.publisso.de/adhoc/uri/RmVlZGVybGUsIFJlZ2luYQ==|https://frl.publisso.de/adhoc/uri/SHNpYSwgSHVuZy1Fbg==|https://frl.publisso.de/adhoc/uri/TGljaHRlbnRoYWxlciwgU3RlZmFuIEYu|https://frl.publisso.de/adhoc/uri/TWVybC1QaGFtLCBKdWxpYW5l|https://frl.publisso.de/adhoc/uri/SGF1Y2ssIFN0ZWZhbmllIE0u|https://frl.publisso.de/adhoc/uri/S3VobG1hbm4sIFRhbmph|https://frl.publisso.de/adhoc/uri/QmF1ZXIsIElzYWJlbCBKLg==|https://frl.publisso.de/adhoc/uri/QmVsdHJhbiwgRWR1YXJkbw==|https://frl.publisso.de/adhoc/uri/R2VyZGVzLCBMaXNhIEFubg==|https://frl.publisso.de/adhoc/uri/TWV6eWRsbywgQWxla3NhbmRyYQ==|https://frl.publisso.de/adhoc/uri/QmFyLU9yLCBBbWl0|https://frl.publisso.de/adhoc/uri/QmFud2VsbCwgQnJlbmRh|https://frl.publisso.de/adhoc/uri/S2hhZGVtaSwgTW9oc2Vu|https://frl.publisso.de/adhoc/uri/T2xzc29uLCBUb21hcw==|https://frl.publisso.de/adhoc/uri/SG9obGZlbGQsIFJlaW5oYXJk|https://frl.publisso.de/adhoc/uri/TGFzc21hbm4sIEhhbnM=|https://frl.publisso.de/adhoc/uri/S8O8bXBmZWwsIFRhbmlh|https://frl.publisso.de/adhoc/uri/S2F3YWthbWksIE5hb3Rv|https://orcid.org/0000-0002-2570-6785
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1000 Erstellt am 2023-11-18T19:43:12.175+0100
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1000 Zuletzt bearbeitet Fri Apr 05 13:09:03 CEST 2024
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