Immune Checkpoint Dysregulation in Aneurysmal Subarachnoid Hemorrhage: A Prospective Study of sCTLA-4 and sPD-L1 as Biomarkers of Symptomatic Vasospasm

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe stroke subtype often complicated by symptomatic cerebral vasospasm (sVP), contributing to delayed cerebral ischemia and poor outcomes. Immune dysregulation, particularly T-cell imbalances and pro-inflammatory cytokines, is implicated in vasospasm development. Soluble immune checkpoint proteins-CTLA-4 (sCTLA-4) and PD-L1 (sPD-L1)-regulate immune homeostasis and may serve as biomarkers or modulators of inflammation in aSAH. This prospective cohort study included 179 aSAH patients, divided into sVP+ (<i>n</i> = 48) and sVP- (<i>n</i> = 131), plus 50 healthy controls. Serum sCTLA-4 and sPD-L1 levels were measured on days 1, 5, and 9 post-ictus using Luminex xMAP. Associations with clinical outcomes were analyzed using non-parametric statistics and hierarchical clustering. Both sCTLA-4 and sPD-L1 were significantly elevated in sVP+ patients versus sVP- and controls, increasing over time. sCTLA-4 was significantly higher in sVP+ on days 5 (<i>p</i> = 0.001) and 9 (<i>p</i> < 0.001), and sPD-L1 on days 5 and 9 (both <i>p</i> < 0.001). Clustering revealed distinct expression patterns between sVP+ and sVP- groups. Elevated sCTLA-4 and sPD-L1 levels are associated with sVP after aSAH and may serve as biomarkers for early immune dysfunction, offering insights into potential therapeutic targets.