Differential Regulation of the Immune System in Peripheral Blood Following Ischemic Stroke

Abstract

AIM. Previous studies have provided insights into complex immune system changes caused by ischemic stroke (IS), while detailed reports are lacking especially in peripheral blood. Here, we sought to identify genetic biomarkers in immune system which significantly associated with the occurrence of IS and explore candidate drugs that can regulate the process. We also investigated whether gene expression alternation of immune genes contributed to differential distribution of immune cells in peripheral blood following IS. Method. 108 IS samples and 47 matched controls were obtained from the GEO database. Immune-related genes (IRGs) and their associated drugs were collected from the ImmPort and PharmGBK databases, respectively. Random forest (RF) regression and least absolute shrinkage and selection operator (LASSO) logistic regression were applied to identify immune-related genetic biomarkers (IRGBs) of IS, and accuracy was verified using neural network models. Finally, proportion changes of various immune cells in peripheral blood of IS patients were evaluated using CIBERSORT and xCell and correlation analyses were performed between IRGBs and differentially distributed immune cells. Results. A total of 537 genes were differentially expressed between IS and control samples. Four immune-related differential expressed genes identified by regression analysis presented strong predictive power ( $\text{AUC}=0.909$ ) which we suggeseted them as immune-related genetic biomarkers (IRGBs). We also demonstrated six immune-related genes targeted by known drugs. In addition, post-IS immune system presented an increase in the proportion of innate immune cells and a decrease in adaptive immune cells in the peripheral circulation, and IRGBs showing significance were associated with this process.Conclusion. The study identified CARD11, ICAM2, VIM, and CD19 as immune-related genetic biomarkers of IS. Six immune-related DEGs targeted by known drugs were found and provide new candidate drug targets for modulating the post-IS immune system. The innate immune cells and adaptive immune cells are diversified in the post-IS immune system, and IRGBs might play important role during this process.