Brain antibodies in the cortex and blood of people with schizophrenia and controls
Glass, LJ and Sinclair, D and Boerrigter, D and Naude, K and Fung, SJ and Brown, D and Catts, VS and Tooney, P and O'Donnell, M and Lenroot, R and Galletty, C and Liu, D and Weickert, TW and Shannon Weickert, C, Brain antibodies in the cortex and blood of people with schizophrenia and controls, Translational psychiatry, 7, (8) pp. 1-9. ISSN 2158-3188 (2017) [Refereed Article]
The immune system is implicated in the pathogenesis of schizophrenia, with elevated proinflammatory cytokine mRNAs found in
the brains of ~ 40% of individuals with the disorder. However, it is not clear if antibodies (specifically immunoglobulin-γ (IgG)) can
be found in the brain of people with schizophrenia and if their abundance relates to brain inflammatory cytokine mRNA levels.
Therefore, we investigated the localization and abundance of IgG in the frontal cortex of people with schizophrenia and controls,
and the impact of proinflammatory cytokine status on IgG abundance in these groups. Brain IgGs were detected surrounding blood
vessels in the human and non-human primate frontal cortex by immunohistochemistry. IgG levels did not differ significantly
between schizophrenia cases and controls, or between schizophrenia cases in ‘high’ and ‘low’ proinflammatory cytokine subgroups.
Consistent with the existence of IgG in the parenchyma of human brain, mRNA and protein of the IgG transporter (FcGRT) were
present in the brain, and did not differ according to diagnosis or inflammatory status. Finally, brain-reactive antibody presence and
abundance was investigated in the blood of living people. The plasma of living schizophrenia patients and healthy controls
contained antibodies that displayed positive binding to Rhesus macaque cerebellar tissue, and the abundance of these antibodies
was significantly lower in patients than controls. These findings suggest that antibodies in the brain and brain-reactive antibodies in
the blood are present under normal circumstances.