Good news!
"In brief
- Stanford researchers discovered that neutrophils, a type of white blood cell, can produce the schizophrenia-associated protein C4A.
- This finding links the increased neutrophil count seen in schizophrenia patients to the disease’s underlying mechanisms.
- The research could lead to novel diagnostic methods and treatments by targeting neutrophil activity and protein production in schizophrenia.
The most common white blood cells in your body – immune cells called neutrophils – can make a protein nobody knew they were making ... That unexpected sighting joins a growing list of hints tying schizophrenia, a disorder of the brain, to events occurring elsewhere in our bodies. ...
Current treatments for schizophrenia are palliatives, Kalinowski said. They don’t stop disease progression or restore motivation or cognitive sharpness. ..."
From the significance and abstract:
"Significance
The number of C4A gene copies is associated with the risk of schizophrenia in genome-wide association studies of individuals with European ancestry.
Higher C4A gene expression is associated with higher levels of synaptic pruning in the brain.
We found that neutrophils from people with schizophrenia show C4 protein amounts that are positively correlated with the number of C4A gene copies.
Neutrophils may gain access to the central nervous system, during some critical periods in the development of schizophrenia. The role of neutrophils both outside the brain in the peripheral circulation and within the brain invites further exploration, potentially leading to new therapeutics.
Abstract
The lack of highly effective disease-modifying treatments for schizophrenia necessitates exploration of novel aspects of its pathophysiology, including attention to innate immune mechanisms outside the brain.
C4 protein activation, associated with the complement cascade of innate immunity, associates with symptoms and predicts outcomes in schizophrenia. However, C4 protein activation does not coincide with expected changes to other proteins in the complement cascade, suggesting another source of C4 protein activation.
Studying a combination of fresh whole blood from 10 anonymous donors and a large set of publicly available microarray data, we show that C4 protein is found and expressed primarily in neutrophils and monocytes.
Then, we compared the correlation between C4 protein in neutrophils, classical monocytes, plasma, and the number of C4A gene copies. We determined the number of C4A genes using digital droplet PCR, C4 protein in neutrophils (15 patients/21 controls) and plasma (30 patients/38 controls) using Western blotting, and classical monocytes (30 patients/38 controls) using flow cytometry.
We found a large positive correlation between the number of C4A gene copies and the amount of C4 protein only in neutrophils and only in the schizophrenia group (Spearman’s rho = 0.63, 95% BCa CI: 0.12 to 0.89, P = 0.012).
Our results indicate a convergence of innate immunity mechanisms associated with schizophrenia. The involvement of innate immunity deserves further attention to determine whether it could be a target for therapy in schizophrenia."
Peripheral complement C4 protein in schizophrenia: Association with gene copy number and immune cell subtypes (open access)
Fig. 2 Neutrophil C4 protein is positively correlated with the number of C4A gene copies in SZ.
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