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

Rohen Harrichandparsad; Gil Lustig; Victoria Sviridchik; Zesuliwe Jule; Mallory Bernstein; Kajal Reedoy; Yashica Ganga; Afrah Khairallah; Farina Karim; Vinod B Patel; Ahmed Iqbal Bhigjee; Duncan Royston; Khadija Khan; Alex Sigal

doi:10.1097/QAD.0000000000004445

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

AIDS. 2026 Jan 15. doi: 10.1097/QAD.0000000000004445. Online ahead of print.

Authors

Affiliations

¹ Department of Neurosurgery, University of KwaZulu-Natal, Durban, South Africa.
² Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
³ The Lautenberg Center for Immunology and Cancer Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
⁴ Africa Health Research Institute and University of KwaZulu-Natal, Durban, South Africa.
⁵ Department of Neurology, University of KwaZulu-Natal, Durban, South Africa.
⁶ Department of Radiology, Lake Smit & Partners.

PMID: 41635057
DOI: 10.1097/QAD.0000000000004445

Abstract

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.

Keywords: CSF proteomics; HIV and aneurysmal subarachnoid haemorrhage; HIV associated neuroinflammation; O-link inflammation panel; endovascular coil embolization.