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Complement-dependent pathogenicity of brain-specific antibodies in cerebrospinal fluid
Nasrin Asgari1, Reza Khorooshi, Søren T Lillevang
1Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsloewsvej 25, DK-5000 Odense C, Denmark.
Journal of Neuroimmunology
|October 4, 2012
Summary
Neurological autoantibodies in cerebrospinal fluid (CSF) can cause pathology. Injecting patient immunoglobulin G with complement into mouse CSF triggered brain damage, demonstrating autoantibodies initiate disease cascades.
Area of Science:
- Neuroimmunology
- Neuropathology
Background:
- Autoantibodies in cerebrospinal fluid (CSF) are linked to neurological diseases, but their causal role remains debated.
- Distinguishing between autoantibodies as a cause or consequence of CNS pathology is critical.
Purpose of the Study:
- To determine if brain-specific autoantibodies alone, when introduced into the CSF, are sufficient to induce neuropathology.
- To investigate the role of complement in antibody-mediated CNS damage.
Main Methods:
- Intrathecal injection of purified immunoglobulin G (IgG) from a neuromyelitis optica patient into the CSF of naïve mice.
- Inclusion or exclusion of complement during the injection.
- Histopathological analysis of brain tissue 7 days post-injection.
Main Results:
- Histopathology revealed damage to the ependyma and disruption of the CSF-brain barrier.
- Pathologic lesions were observed distant from the injection site.
- No pathology was observed in mice that received IgG without complement.
Conclusions:
- Autoantibodies and complement in the CSF are sufficient to initiate a pathogenic cascade in the brain.
- This finding supports a causal role for autoantibodies in certain neurological diseases.
- Complement activation is essential for antibody-induced neuropathology.
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