Abstract TMP24: Soluble St2 Links Innate Inflammation to Secondary Injury After Stroke and Subarachnoid Hemorrhage

Abstract

Background: We recently found that soluble ST2 (sST2) is a plasma marker that predicts neurological outcome after ischemic stroke and aneurysmal subarachnoid hemorrhage. We sought to extend these findings by studying sST2 associations with markers of secondary brain injury and peripheral innate immunity. Methods: We studied 241 acute ischemic stroke (AIS) patients with sST2 level measured on admission (7.4 ± 3.7 hrs after stroke onset) and at least one follow-up brain imaging study, obtained at a mean of 2.2 ± 1.4 days after stroke onset. A subgroup (n=147) had a second sST2 measurement at a mean of 2.1 ± 1.7 days after stroke onset. A separate cohort of 110 subarachnoid hemorrhage (SAH) patients were studied who had plasma sST2 measured at approximately 3.5 ± 1.2 days after ictus. Markers of secondary brain injury included edema after AIS (midline shift), and delayed cerebral ischemia (DCI) or epileptiform discharges on EEG after SAH. The relationships between sST2 level and outcome measures were assessed. Primary blood mononuclear cells from SAH patients and elective aneurysm controls were analyzed by multiparameter flow cytometry to phenotype the peripheral immune response. Results: In the AIS cohort, baseline plasma sST2 level was associated with the presence of midline shift (46.1 vs. 41.8 ng/mL, p=0.017), which further increased at 48 hr after stroke onset (50.6 vs. 38.4 ng/mL, p=0.006). In the SAH cohort, median sST2 in patients who developed new epileptiform abnormalities was higher compared to patients who did not (114.8 ng/ml vs. 74.7 ng/ml, p=0.024). Higher median sST2 concentration was also observed in those patients with DCI (90.8 vs 53.7ng/mL, p=0.003). In patients with high sST2, flow cytometry identified a peripheral monocyte population with decreased expression of CD14 (4.27x105 ± 2950 A.U. vs. 5.64x105 ± 1290 A.U., p<0.001), and increased expression of CD16 (39,960 ± 272 A.U. vs. 34,869 ± 183 A.U., p<0.001). Conclusion: Plasma sST2 independently predicts edema after stroke, and DCI and epileptiform abnormalities after subarachnoid hemorrhage. Elevated sST2 is also associated with changes in peripheral innate immune cells. These data suggest that sST2 links the innate immune response to secondary brain injury.