Increased activation product of complement 4 protein in plasma of individuals with schizophrenia

• DOI: 10.1038/s41398-021-01583-5
• Publication Date: 2021-09-22T06:03:05Z
• Authors: Agnieszka Kalinowski; Joanna Liliental; Lauren A. Anker; Omer Linkovski; Collin Culbertson; Jacob N. Hall; Reenal Pattni; Chiara Sabatti; Douglas Noordsy; Joachim F. Hallmayer; Elizabeth D. Mellins; Jacob S. Ballon; Ruth O’Hara; Douglas F. Levinson; Alexander E. Urban
• Keywords: C4A; Anaphylatoxin

Abstract Structural variation in the complement 4 gene ( C4 ) confers genetic risk for schizophrenia. The includes numbers of increased C4A copy number, which predicts mRNA expression. C4-anaphylatoxin (C4-ana) is a protein fragment released upon activation that has potential to change blood–brain barrier (BBB). We hypothesized elevated plasma levels C4-ana occur individuals with schizophrenia (iSCZ). Blood was collected from 15 iSCZ illness duration < 5 years and 14 healthy controls (HC). Plasma measured by radioimmunoassay. Other products C3-ana, C5-ana, terminal complex (TCC) were also measured. Digital-droplet PCR used determine structural state. Recombinant added primary brain endothelial cells (BEC) permeability vitro. concentration compared HC (mean = 654 ± 16 ng/mL, 557 94 respectively, p 0.01). patients carried more copies C4AL demonstrated positive correlation between concentrations number. Furthermore, monolayer BEC Our findings are consistent specific role raise possibility its product, C4-ana, increases BBB permeability. Exploratory analyses suggest novel hypothesis relationship number could be altered iSCZ, suggesting an interaction unknown and/or environmental factors.