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 undergoing clinically indicated lumbar puncture as part of workup for a non-neurovascular condition (n=9). Methods We performed lumbar puncture and analyzed CSF samples from individuals presenting with aneurysmal SAH (n=30) and PLWH without any known vascular pathology (n=9). Among aneurysm patients, 13 were PLWH and 17 were HIV-negative. An Olink Target 96 Inflammation panel was used to quantify inflammatory proteins. Results We assessed inflammatory profiles in cerebrospinal fluid (CSF) using Olink proteomics in individuals with ruptured anterior communicating artery aneurysms, with and without HIV infection. Among 68 detectable inflammatory proteins, 43 were significantly upregulated in participants with aneurysms (n=30) compared to people living with HIV (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 aneurysm is associated with strong upregulation of inflammatory proteins in the CSF. This inflammatory response appears largely independent of HIV infection.