Stanford Finds Neutrophils Produce Schizophrenia Risk Protein C4A in 1% Disorder
Updated
Updated · BIOENGINEER.ORG · May 19
Stanford Finds Neutrophils Produce Schizophrenia Risk Protein C4A in 1% Disorder
5 articles · Updated · BIOENGINEER.ORG · May 19
Stanford Medicine researchers found neutrophils—not just the liver—produce complement protein C4A, a major genetic schizophrenia risk factor, pointing to a peripheral immune source for disease-linked complement activity.
Blood samples showed schizophrenia patients had higher C4A gene expression in neutrophils that tracked with symptom severity, but lower intracellular protein, suggesting the cells may be secreting or consuming more C4A outside the cell.
That pattern could help explain elevated plasma C4-ana and broader complement activation already seen in schizophrenia, tying immune-cell activity to synaptic pruning, cortical thinning and cognitive deficits.
The finding also reframes clozapine’s neutrophil-suppressing effect and raises the prospect of blood-based biomarkers and treatments that target neutrophils or complement outside the brain.
Will a simple blood test soon reveal who is at risk for schizophrenia?
Is schizophrenia not a brain disorder, but an immune disease that attacks the brain?
From Blood to Brain: Neutrophil C4A Overproduction as a Key Driver of Synaptic Loss and a New Era in Schizophrenia Care
Overview
In May 2026, Stanford Medicine made a groundbreaking discovery that fundamentally changed our understanding of schizophrenia. Researchers found that neutrophils, a type of white blood cell, play a critical role in the disease by acting as 'peripheral factories' for the protein C4A. C4A is known as the strongest common genetic risk factor for schizophrenia and is crucial for the brain's synaptic pruning process, which refines neural networks and sharpens thinking. This discovery established a direct link between the immune system and schizophrenia, revealing how immune activity outside the brain can drive changes that lead to the disorder.