Shared dysregulation of complement and phosphorylation pathways in the cerebrospinal fluid of encephalitis, Aicardi–Goutières syndrome, and autism

Brain inflammation is increasingly recognized across childhood brain disorders, including infections of the brain (encephalitis), autism spectrum disorder (ASD), and a rare genetic condition called Aicardi-Goutières syndrome (AGS). AGS causes the body's antiviral defences to switch on inappropriately, attacking the developing brain. It has not been clear whether these conditions share common biological features. Researchers examined cerebrospinal fluid (the fluid surrounding the brain and spinal cord) from children with encephalitis, AGS, and ASD, comparing each group with children who had non-inflammatory neurological conditions. Using protein-analysis technology, they measured which proteins were present at higher or lower levels than expected. Each condition showed its own distinct pattern. Children with encephalitis had signs of active immune response and antibody production, alongside lower levels of proteins that support brain energy use and nerve connections. Children with AGS showed activation of antiviral immune pathways and changes in proteins involved in brain structure. Children with ASD had increased levels of proteins involved in tissue structure and protection against cell damage, with lower levels of certain stress-response proteins. Importantly, all three conditions shared one thing in common: activation of the complement system, a part of the immune system that normally helps fight infection but can also damage healthy tissue when overactive. Four specific complement proteins were consistently elevated across all groups. This suggests that different childhood brain conditions, despite very different causes, may share an underlying immune mechanism. It also points to complement proteins as promising candidates for future tests to help diagnose or monitor these conditions. Further research is needed before this translates into new treatments or clinical tests.