Abstract
Background: Advancing age is associated with changes to the immune system, which affect stroke outcome. We previously demonstrated an age-associated alteration in leukocyte gene expression in patients with ischemic stroke. The aim of this study is to validate these findings in an independent stroke cohort and assess the relationship to stroke outcome. Methods: Genes associated with age were identified in a cohort of 57 patients with acute ischemic stroke. Peripheral blood RNA was measured using whole genome microarrays and genes associated with advancing age identified (FDR-corrected p < 0.05, partial correlation coefficient r > |0.3|); age-associated gene expression differences in patients with poor 90-day outcome (mRS < 2) were also compared. Genes were functionally characterized by pathway and enrichment analysis and verified against age-associated genes from two additional stroke cohorts containing a total of 173 patients. Results: There were 536 genes associated with age in the new stroke cohort, of which 286 decreased and 253 increased with age. Thirty-nine (39) of the age-associated genes were present in previous stroke cohorts analyzed, including a decrease in CCR6, CXCR5, BLNK and NT5E. A decrease in CXCR5 and CD79B was also identified in patients with poor outcome. Pathways and enriched terms relating to the humoral adaptive system immune system, including B-cell and lymphocyte activation, were among those represented in age-associated genes. Conclusions: Age-related changes in leukocyte gene expression were validated in an independent cohort of patients with ischemic stroke. Verified changes include alterations to the humoral immune system and a relationship to stroke outcome. Further investigation of the aging immune system in stroke is warranted.
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