Cerebrospinal fluid proteomics reveals inflammatory activation in aneurysmal subarachnoid hemorrhage irrespective of HIV status

Objectives: – People living with HIV (PLWH) are at increased risk of cerebrovascular abnormalities, including aneurysmal subarachnoid hemorrhage (SAH). However, it is unclear whether HIV-associated inflammation contributes significantly to the inflammatory response observed in the cerebrospinal fluid (CSF) during aneurysm rupture. Here, we used high-throughput Olink proteomics to compare inflammatory marker profiles in CSF between participants with aneurysmal SAH and PLWH without aneurysms. Design: – This was a cross-sectional observational study which enrolled participants who were indicated for endovascular coil embolisation due to ruptured anterior communicating artery aneurysms (n = 30) or who underwent clinically indicated lumbar puncture as part of the workup for non-neurovascular conditions (n = 9). Methods: – We performed a lumbar puncture and analyzed CSF samples from individuals presenting with aneurysmal SAH (n = 30) and PLWH without any known vascular pathology (n = 9). Among the aneurysm patients, 13 were PLWH and 17 were HIV-negative. An Olink Target 96 Inflammation panel was used to quantify inflammatory proteins. Results: – Among 68 detectable inflammatory proteins, 43 were significantly upregulated in participants with aneurysms (n = 30) compared to PLWH without aneurysm (n = 9). A similar inflammatory signature was observed in HIV-negative aneurysm participants (n = 17) and PLWH with aneurysm (n = 13), with no significant differences between these two groups. Interleukin-6 (IL-6) was the most upregulated protein across all aneurysm to non-aneurysm comparisons. These findings suggest that aneurysm rupture is associated with a strong CSF inflammatory response, largely independent of HIV status. Conclusion: – Ruptured intracranial aneurysms are associated with strong upregulation of inflammatory proteins in the CSF. This inflammatory response appears independent of HIV infection.