Proteomic profiling identifies systemic drivers of blood-brain barrier injury in sickle cell disease.

Elevated blood-brain barrier permeability in sickle cell disease correlates with microstructural brain injury, with 79 plasma proteins linked to systemic pathways influencing BBB disruption.

• Why it matters: Understanding how systemic inflammation and endothelial injury contribute to BBB disruption is crucial for addressing brain injury and cognitive deficits in sickle cell disease, yet this relationship remains poorly characterized.
• What they did: The study used dynamic contrast-enhanced MRI to measure BBB permeability in 37 adults with SCD and 37 controls, alongside plasma proteomics and network analysis to identify systemic drivers of BBB injury.
• The result: Findings show increased BBB permeability in SCD is associated with tissue hypoxia and microstructural damage, mediated by proteins involved in iron homeostasis, hypoxia response, and immune regulation, suggesting potential therapeutic targets.