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01.12.2018 | Short report | Ausgabe 1/2018 Open Access

Journal of Neuroinflammation 1/2018

Selective localization of IgG from cerebrospinal fluid to brain parenchyma

Zeitschrift:
Journal of Neuroinflammation > Ausgabe 1/2018
Autoren:
Marlene Thorsen Mørch, Sofie Forsberg Sørensen, Reza Khorooshi, Nasrin Asgari, Trevor Owens

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.
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