Introduction:
Immune system dysregulation occurs with age. This includes an increase in inflammation, and immunosenescence, the inability to efficiently respond to new immune challenges. These changes are evident in various diseases but have yet to be evaluated in a population with ischemic stroke. Age is an important factor in stroke, contributing to stroke risk, outcome and risk of hemorrhagic transformation. This study aimed to assess the changes that occur with age in the leukocyte gene expression of patients with ischemic stroke.
Methods:
Two cohorts of acute ischemic stroke patients were analyzed; cohort 1 (n=94) and cohort 2 (n=79). RNA was isolated from PAXgene tubes and processed on Affymetrix microarrays. Differentially expressed genes associated with age quartiles were identified by ANCOVA, adjusted for sex and batch. Functional analysis identified age-associated pathways. Differentially expressed genes were compared with previous non-stroke aging studies in whole blood.
Results:
There were 61 and 442 age-associated genes in cohorts 1 and 2 respectively (FDR-corrected p<0.05, partial correlation coefficient ≥ |0.3|). Nineteen genes, including
CR2, CCR6
and
CXCR5
, were found in common and decreased with age among both cohorts (max-log10(p value) = 17). Functional analysis of the 61 and 442 genes revealed with advancing age there is a change in the humoral immune system, including antibody production and B cell proliferation. When compared to aging gene expression studies in controls, 52% of age-associated genes in cohort 1 and 31% of cohort 2 age-associated genes overlapped with those found in controls, and 16 of the 19 common genes to both cohorts overlapped in controls (max-log10(p value) = 15).
Conclusion:
In patients with acute stroke there is a change in leukocyte gene expression with advancing age. Changes included a shift in humoral immune response with a potentially impaired B cell response. While many of the age-associated alterations in gene expression present in stroke are similar to non-stroke controls, these changes warrant further investigation for their impact on stroke outcome and risk.