Selective localization of IgG from cerebrospinal fluid to brain parenchyma

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Abstract

Background: Encounter of autoantibodies with specific antigens can lead to hypersensitivity reactions and pathology. In multiple sclerosis and neuromyelitis optica spectrum disease (NMOSD), immunoglobulin-G (IgG) deposition has been observed in pathological lesions in the central nervous system. The paradigmatic autoantibodies in NMOSD are specific for the water channel aquaporin-4, localized to astrocytic end-feet at the blood-brain barrier and ependymal cells at the cerebrospinal fluid-brain barrier. We have previously observed that IgG antibodies from NMO patients (NMO-IgG) access brain parenchyma from the cerebrospinal fluid and induce subpial and periventricular NMO-like lesions and blood-brain barrier breakdown, in a complement-dependent manner. Objective: To investigate how IgG trafficking from cerebrospinal fluid to brain parenchyma can be influenced by injury. Methods: IgG from healthy donors was intrathecally injected into the cerebrospinal fluid via cisterna magna at 1, 2, 4, or 7 days after a distal stereotactic sterile needle insertion to the striatum. Results: Antibody deposition, detected by staining for human IgG, peaked 1 day after the intrathecal injection and was selectively seen close to the needle insertion. When NMO-IgG was intrathecally injected, we observed complement-dependent NMO-like pathology (loss of aquaporin-4 and glial fibrillary acidic protein) proximal to the insertion site, with similar kinetics. A fluorescent tracer did not show the same distribution indicating IgG-selective localization. Conclusion: These findings suggest that IgG from cerebrospinal fluid localize selectively in brain parenchyma at the site of injury and pathogenic NMO-IgG induce astrocyte pathology at the same location.

Original languageEnglish
Article number110
JournalJournal of Neuroinflammation
Volume15
Number of pages8
ISSN1742-2094
DOIs
Publication statusPublished - 17. Apr 2018

Keywords

  • Cerebrospinal fluid
  • Deposition
  • Immunoglobulin-G
  • Neuromyelitis optica spectrum disorders
  • Pathology
  • Protein Transport/drug effects
  • Humans
  • Mice, Inbred C57BL
  • Neuromyelitis Optica/metabolism
  • Aquaporin 4/immunology
  • RNA, Messenger/metabolism
  • Glial Fibrillary Acidic Protein/metabolism
  • Immunoglobulin G/administration & dosage
  • Central Nervous System/anatomy & histology
  • Animals
  • Parenchymal Tissue/metabolism
  • Time Factors
  • Dextrans/metabolism
  • Cytokines/genetics
  • Female
  • Mice

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