Selective localization of IgG from cerebrospinal fluid to brain parenchyma

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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.

OriginalsprogEngelsk
Artikelnummer110
TidsskriftJournal of Neuroinflammation
Vol/bind15
Antal sider8
ISSN1742-2094
DOI
StatusUdgivet - 17. apr. 2018

Fingeraftryk

Cerebrospinal Fluid
Neuromyelitis Optica
Pathology
Needles
Cisterna Magna
Glial Fibrillary Acidic Protein
Wounds and Injuries
Hypersensitivity
Central Nervous System

Citer dette

@article{711fa6420be84cc59fdd136f6d466d22,
title = "Selective localization of IgG from cerebrospinal fluid to brain parenchyma",
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.",
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",
author = "M{\o}rch, {Marlene Thorsen} and {Forsberg S{\o}rensen}, Sofie and Khorooshi, {Reza M. H.} and Nasrin Asgari and Trevor Owens",
year = "2018",
month = "4",
day = "17",
doi = "10.1186/s12974-018-1159-8",
language = "English",
volume = "15",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Selective localization of IgG from cerebrospinal fluid to brain parenchyma

AU - Mørch, Marlene Thorsen

AU - Forsberg Sørensen, Sofie

AU - Khorooshi, Reza M. H.

AU - Asgari, Nasrin

AU - Owens, Trevor

PY - 2018/4/17

Y1 - 2018/4/17

N2 - 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.

AB - 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.

KW - Cerebrospinal fluid

KW - Deposition

KW - Immunoglobulin-G

KW - Neuromyelitis optica spectrum disorders

KW - Pathology

KW - Protein Transport/drug effects

KW - Humans

KW - Mice, Inbred C57BL

KW - Neuromyelitis Optica/metabolism

KW - Aquaporin 4/immunology

KW - RNA, Messenger/metabolism

KW - Glial Fibrillary Acidic Protein/metabolism

KW - Immunoglobulin G/administration & dosage

KW - Central Nervous System/anatomy & histology

KW - Animals

KW - Parenchymal Tissue/metabolism

KW - Time Factors

KW - Dextrans/metabolism

KW - Cytokines/genetics

KW - Female

KW - Mice

U2 - 10.1186/s12974-018-1159-8

DO - 10.1186/s12974-018-1159-8

M3 - Journal article

C2 - 29665816

VL - 15

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

M1 - 110

ER -