Abstract WP133: Sex Differences in the Human Intracerebral Hemorrhage Peripheral Blood Transcriptome Implicate Differential Immune and Inflammatory Responses

Sex differences in immune and inflammatory pathways have been shown in health and disease. However, little research has been done on sex differences following human Intracerebral Hemorrhage (ICH). We sought to unveil transcriptome differences in blood between Male (M) and Female (F) ICH responses. We evaluated 33 ICH patients and 33 vascular risk factor matched controls (VRFC), 9F and 24M each. Peripheral blood expression of 21,175 genes was analyzed at the co-expression network level with WGCNA - separate F (F-ICH and F-VRFC) and M (M-ICH and M-VRFC) networks generated; and per gene level (ANCOVA: Age, Time, and Sex*Dx (Diagnosis)). Five F (F-6, F-20, F-21, F-19, F-5) and 2 M (M-32, M-26) WGCNA modules were significant to Dx (p < 0.05) (Fig 1A). 105 genes were significant for the direct comparison (F-ICH vs M-ICH p < 0.05, |FC| > 1.2; Sex*Dx FDR < 0.2), which separated Sex*Dx groups (Fig 1B). 1,425 genes were differentially expressed in F-ICH (F-ICH vs F-VRFC p < 0.05, |FC| > 1.2; Sex*Dx FDR < 0.2) and 421 in M-ICH (M-ICH vs M-VRFC p < 0.05, |FC| > 1.2; Sex*Dx FDR < 0.2) (Fig 1C). F-ICH response was enriched in Monocyte and T Cell Specific genes and M-ICH in B Cell and Erythroblast specific genes; both were enriched in Neutrophil specific genes (Fig 1A). Overall, F modules and gene lists were significantly enriched in 236 GO terms (FDR < 0.1) and M modules in 55; 20 were common (Fig 1D). The ICH response unique to F-ICH included Inflammatory Response, T Cell Activation, Autophagy, Apoptotic Process, and RNA Splicing. M-ICH unique included B Cell Receptor Signaling, Immunoglobulin Receptor Binding, Antigen Binding, Complement Activation, and Receptor Mediated Endocytosis. Common responses included Innate Immune Response, Blood Coagulation, and Fc-ã Receptor Signaling Involved in Phagocytosis (Fig 1E). We found sex differences in ICH transcriptome responses in human peripheral blood. These implicate specific cell types in each sex that could represent novel sex-specific treatment targets.