Abstract WP208: Cd14+ Monocytes Mediate The Immunological Environment In Aneurysmal Subarachnoid Hemorrhage Through Cxcl10 Secretion

Abstract

Introduction: Robust evidence suggest that aneurysmal subarachnoid hemorrhage (aSAH) triggers a potent respone from innate and adaptive inmunities. An increase in CD8+CD161+ cells has been observed in the acute phase of patients with aSAH. However, the role of this cells is poorly understood. Methods: Cerebrospinal fluid of patients with aSAH and non-aneurysmal SAH (nasSAH) was analyzed. Single cell RNA sequencing (scRNAseq) of CD8+CD161+ cells sorted from the CSF of patients with aSAH was performed. Specific cell populations were identified based on gene clustering. Additionaly ten genes were identified. The levels of these genes were then quantified with real-time quantitative polymerase chain reaction (RT- qPCR) and were compared in patients with aSAH and patients with naSAH. Finally highly expressed proteins were quantified with ELISA. Results: Gene clustering suggested that CD14+ monocytes, NK cells and T cells expressed CD8+CD161+ in the CSF of patients with aSAH. Ten differentially expressed genes of clinical interest were then identified: CCL55, CCL7, APOE, SPP1, CXCL8, CXCL10, HMOX1, LTB, MAL, HLA-DRA1/HLA-DRB1 and their mRNA levels were quantied. CXCL10 and HMOX1 levels were higher in aSAH samples than in naSAH (p=0.02 and p=0.076, respectively). CXCL10 was the most significantly different expressed gene in aSAH compared to naSAH samples, and it was chosen for further analysis with ELISA. Protein levels of CXCL10 were higher in patients with aSAH [median(IQR) = 598(635) pg/mL] compared to patients with naSAH [median(IQR) = 31(214) pg/mL, p=0.04]. Conclusion: CD14+ monocytes, NK cells and T cells are CD8+CD161+ in patients with aSAH. CD14+ may be involved in the inflammatory response after aSAH through the expression of the pro-inflammatory cytokine CXCL10.