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

OBJECTIVES: People with HIV (PWH) 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 PWH without aneurysms. DESIGN: This was a cross-sectional observational study which enrolled participants who were indicated for endovascular coil embolization due to ruptured anterior communicating artery aneurysms ( n = 30) or who underwent clinically indicated lumbar puncture as part of the workup for nonneurovascular conditions ( n = 9). METHODS: We performed a lumbar puncture and analyzed CSF samples from individuals presenting with aneurysmal SAH ( n = 30) and PWH without any known vascular disorder ( n = 9). Among the aneurysm patients, 13 were PWH 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 PWH without aneurysm ( n = 9). A similar inflammatory signature was observed in HIV-negative aneurysm participants ( n = 17) and PWH 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 nonaneurysm 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.