ABSTRACT NUMBER: ESOC2026A2338 ACUTE-PHASE TRANSCRIPTOMIC SIGNATURES IN YOUNG ADULTS WITH CRYPTOGENIC ISCHEMIC STROKE

Abstract Background and aims Stroke in young adults often remains cryptogenic despite thorough diagnostic work-up. Our aim was to identify differentially expressed genes and biological pathways active in the acute phase of cryptogenic stroke using RNA sequencing from peripheral blood. Methods Patients aged 18–54 with cryptogenic stroke (n=48), included in the Estonian Young Stroke Registry, had blood samples collected within 72 hours of stroke onset and at 1-year follow-up. After quality control, 41 patients were included for transcriptome analysis (mRNA). Median age was 46 years, IQR 13; 66% male; median NIHSS score 3, IQR 4. Differential expression analysis was performed using DESeq2 (adjusted p-value <0.05), using unpaired and paired design. Pathway analysis was based on full gene lists of up- or downregulated genes. Results Analysis revealed that upregulated genes formed a dense network enriched for innate immune activation, including toll-like receptor signaling and leukocyte recruitment. The most significant and consistently upregulated genes across both unpaired and paired analyses included TLR2, NFKBIA, and ANAPC15. In contrast, downregulated genes were enriched for pathways related to cellular maintenance, transcriptional regulation, and cell proliferation, with representative examples including XPO1, CRY1, and MAF which were reproducibly downregulated in both analytical approaches. Conclusions The acute phase of cryptogenic stroke is characterized by innate immune activation and concurrent downregulation of proliferation- and maintenance-related processes. These findings provide molecular insight into cryptogenic stroke pathophysiology in young adults. Conflict of interest Nothing to disclose