Evaluating histone H3.1 as a biomarker for acute ischemic stroke: insights into NETs and stroke pathophysiology

The diagnosis of acute ischemic stroke (AIS) can be challenging when neuroimaging findings are normal or equivocal. Neutrophil extracellular traps (NETs), particularly histone H3.1, have potential as biomarkers for AIS. This study evaluated NETs, specifically histone H3.1, as diagnostic biomarkers for AIS. This prospective study included 89 patients with AIS and 20 healthy controls. Plasma histone H3.1 levels were measured using the Nu.Q® H3.1 enzyme-linked immunosorbent assay (ELISA). Seven cytokines were analyzed using a bead-based immunoassay. Statistical analyses were used to compare histone H3.1 levels between groups and evaluate correlations with clinical parameters and cytokines. Histone H3.1 levels were significantly higher in patients with AIS (271.05 ± 33.40 ng/mL) versus controls (95.33 ± 12.86 ng/mL, p < 0.001). Multivariable logistic regression identified H3.1 as an independent risk factor for AIS (p = 0.006), with an area under the curve of 0.907. Significant correlations were found between H3.1, interleukin-6 (0.290, p = 0.013) and vascular cell adhesion molecule 1 (0.297, p = 0.011). In conclusion, the NETs H3.1 ELISA test is a reliable new diagnostic option that supports the diagnosis of AIS.