title: Elevated levels of autoantibodies targeting the M1 muscarinic acetylcholine receptor and neurofilament medium in sera from subgroups of patients with schizophrenia.
abstract: 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.
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Jones
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane, Australia; The University of Queensland, Queensland Centre for Mental Health Research Brisbane, Australia.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Mowry
authors.affiliation: The University of Queensland, Queensland Centre for Mental Health Research Brisbane, Australia.
authors.forename: Duncan E
authors.initials: DE
authors.lastname: McLean
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane, Australia.
authors.forename: Basil X
authors.initials: BX
authors.lastname: Mantzioris
authors.affiliation: The University of Queensland, School of Medicine, Brisbane, Australia; Department of Neurology, Royal Brisbane & Women's Hospital, Brisbane, Australia.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Pender
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia. Electronic address: j.greer@uq.edu.au.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Greer
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000097:blood* / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D043643:Receptor, Muscarinic M1 / Q000097:blood* / Q000235:genetics; D012559:Schizophrenia / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D016900:Neurofilament Proteins; D043643:Receptor, Muscarinic M1; C061195:neurofilament protein M
keywords: Autoantibodies; Immunohistochemistry; M1 muscarinic acetylcholine receptor; Neurofilament medium (NFM); Schizophrenia