Elevated levels of autoantibodies targeting the M1 muscarinic acetylcholine receptor and neurofilament medium in sera from subgroups of patients with schizophrenia

Jones, Amanda L., Mowry, Bryan J., McLean, Duncan E., Mantzioris, Basil X., Pender, Michael P. and Greer, Judith M. (2014) Elevated levels of autoantibodies targeting the M1 muscarinic acetylcholine receptor and neurofilament medium in sera from subgroups of patients with schizophrenia. Journal of Neuroimmunology, 269 1-2: 68-75. doi:10.1016/j.jneuroim.2014.02.008


Author Jones, Amanda L.
Mowry, Bryan J.
McLean, Duncan E.
Mantzioris, Basil X.
Pender, Michael P.
Greer, Judith M.
Title Elevated levels of autoantibodies targeting the M1 muscarinic acetylcholine receptor and neurofilament medium in sera from subgroups of patients with schizophrenia
Journal name Journal of Neuroimmunology   Check publisher's open access policy
ISSN 0165-5728
1872-8421
Publication date 2014-04-15
Sub-type Article (original research)
DOI 10.1016/j.jneuroim.2014.02.008
Open Access Status
Volume 269
Issue 1-2
Start page 68
End page 75
Total pages 8
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2015
Language eng
Formatted abstract
Highlights
• We tested for anti-brain autoantibodies in sera of SZ patients and controls.
• Antibodies from SZ patients targeted cells & filamentous structures in the brain.
• Cell body antibodies correlated with worse SZ negative symptom scores.
• Potential targets of anti-filamentous structure antibodies were identified.
• Results support the hypothesis that autoantibodies play a role in some cases of SZ.

Schizophrenia is a severe debilitating brain disorder with a poorly understood aetiology. Among the diverse aetiological clues lies evidence for immune abnormalities in some individuals. The aim of this study was to investigate the frequency and specificity of autoantibodies directed against the brain in people with schizophrenia. Sera were screened for reactivity against human brain tissue (hippocampus and prefrontal cortex). Neuronal cell body and filamentous patterns of brain tissue staining were observed significantly more frequently in sera from schizophrenia patients (n = 30) compared to controls (n = 24). Sera that showed a neuronal cell body pattern of staining on hippocampus reacted strongly to an extracellular epitope of the M1 muscarinic acetylcholine receptor (m1AChR) in ELISA. Both cell body staining and elevated m1AChR reactivity correlated with higher symptom scores for poverty of speech. Sera showing a filamentous staining pattern predominantly targeted microfilaments, intermediate filaments or neurofilaments, particularly neurofilament medium (NFM), which is a dopamine receptor interacting protein. By ELISA, there was strongly elevated reactivity against NFM in a subset (15%) of schizophrenia patients (n = 101) compared to healthy controls (n = 55) or patients with multiple sclerosis (n = 32). These results support the hypothesis that neurotransmitter receptors or molecules involved in regulation of neurotransmission are targets of autoantibodies in some people with schizophrenia.
Keyword Schizophrenia
Autoantibodies
Immunohistochemistry
Neurofilament medium (NFM)
M1 muscarinic acetylcholine receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Mon, 17 Mar 2014, 14:18:39 EST by Judith M Greer on behalf of UQ Centre for Clinical Research