Early changes in inflammation-related proteins in the cerebrospinal fluid and plasma of patients with aneurysmal subarachnoid hemorrhage

Topic/Product:
Inflammation, Inflammation Panel 250
Disease Area:
Subarachnoid Hemorrhage (SAH)
Sample Type:
CSF

Highlights

  • NULISAseq platform was used for the analysis of early phase (<72 hr) changes in neuroinflammatory proteins in plasma and CSF from aSAH patients. We identified over 107 cytokines significantly elevated in plasma from aSAH patients versus controls.
  • A smaller portion of these (22) showed significant correlations between plasma and CSF levels within aSAH patients.
  • Three cytokines were identified that are significantly different in aSAH versus control plasma, are significantly correlated with CSF levels in aSAH patients, and vary with time in CSF during the first 72 h post-injury: CXCL12, SAA1, and IL-15.

Abstract

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is a relatively uncommon but high mortality form of stroke that can result in long-lasting disability. A better understanding of key neuroinflammatory changes during the early phase (<72 h) may provide potential avenues of treatment.

Methods

In an attempt to understand these early changes, we recruited 7 aSAH patients for profiling of longitudinal plasma and cerebrospinal fluid (CSF) proteins at up to 72 h post injury. We additionally compared this to control plasma obtained previously from healthy elderly volunteers. Using the Alamar Biosciences NULISAseq platform, we obtained a comprehensive picture of early peripheral and central inflammatory changes after injury.

Results

This study demonstrated very early plasma changes across 107 inflammatory proteins, 22 of which showed significant correlations between plasma and CSF. Of these, CXCL12, IL-15, and SAA1 are detectably elevated <24 h in plasma, significantly correlated with CSF levels, and altered as a function of aSAH progression over time during this early phase.

Conclusion

This study demonstrates the feasibility of measuring a large number of inflammatory proteins in CSF and plasma from aSAH patients soon after injury. Despite the small sample size and limitations of the control group, we identified several previously reported “hits” that may offer prognostic utility and/or therapeutic potential for aSAH patients: CXCL12, IL-15, and SAA1.

Authors & Affiliations

David J. Braun, PhD a,b Robert M. Flight, PhD e Josh M. Morganti, PhD , Kevin W. Hatton, MD, PhD, FCCM , Hunter N.B. Moseley, PhD f c , Justin F. Fraser, MD , Caleb S. Bailey, PhD a,b , Bingqing Zhang, PhD g , Ishara S. Ariyapala, PhD a , g b,d , , Tae K. Kim, PhD Linda J. Van Eldik, PhD a a,b,*

Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA b c d e f g Department of Neuroscience, University of Kentucky, Lexington, KY 40536, USA Department of Anesthesiology, University of Kentucky, Lexington, KY 40536, USA Departments of Neurosurgery, Neurology, Radiology, Otolaryngology, University of Kentucky, Lexington, KY 40536, USA Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA Department of Molecular & Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA Alamar Biosciences, Fremont, CA 94538, USA

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.