Evaluation of Dried Plasma Spot-Based Quantification of Glial Fibrillary Acidic Protein as a Disease-Associated Biomarker in Neuromyelitis Optica Spectrum Disorder

Product:
GFAP AQ Singleplex
Topic:
Neurology
Disease Area:
Healthy Aging
Sample Type:
Dried Plasma Spot (DPS)
Product:
GFAP AQ Singleplex
Topic:
Neurology
Disease Area:
Healthy Aging
Sample Type:
Dried Plasma Spot (DPS)

Abstract

Objective

To evaluate the diagnostic accuracy of glial fibrillary acidic protein (GFAP) measured in dried plasma spots versus conventional plasma- and serum-GFAP testing for assessment of disease severity in aquaporin-4 immunoglobulin G–positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD).

Methods

A neuroimmunological prospective cohort of remission samples from 70 participants with the diagnoses AQP4-IgG+ NMOSD (n = 19), myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD; n = 9), relapsing–remitting multiple sclerosis (RRMS; n = 28) and healthy controls (HC; n = 14) from a single center were included. GFAP concentrations were measured in frozen and thawed plasma and paired dried plasma spot (DPS) samples using an ultrasensitive proximity ligation–based assay (nucleic acid–linked immuno-sandwich assay; NULISA). In NMOSD, GFAP was additionally quantified in paired serum samples using a single-molecule array (Simoa) assay as a reference. Cross-matrix correlations, diagnostic performance, and associations with neurological disability were evaluated.

Results

GFAP concentrations measured by NULISA correlated strongly between plasma and DPS samples across diagnostic groups and healthy controls. In NMOSD, plasma GFAP measured by NULISA showed strong concordance with serum GFAP quantified by Simoa. DPS-derived and plasma-derived GFAP demonstrated good diagnostic accuracy for AQP4-IgG+ NMOSD and was significantly associated with neurological disability as measured by the Expanded Disability Status Scale (EDSS). Group-wise comparisons across plasma and DPS showed retained elevation of GFAP in AQP4-IgG+ NMOSD compared with the other diagnostic groups and healthy controls.

Interpretation

GFAP quantification using the NULISA platform is feasible in plasma and DPS samples and enables reliable biomarker assessment in a potentially remote-compatible setting. DPS-derived GFAP measurements retained meaningful information on disability in NMOSD and may provide an analytical framework for future studies evaluating minimally invasive capillary or self-sampling approaches.

Authors and Affiliations

Felix Wohlrab¹, Evelyn Alvarez², Roua Hamdi¹, Bingqing Zhang², Hayeun Ji², Niyati Jhaveri², Patrick Schindler³˒⁴, Pedro Sanchez³, Pia S. Sperber³˒⁴, Tanja Schmitz-Hübsch³, Frederike C. Oertel¹˒⁴˒⁵, Nisa Vorasoot⁶, Najib Kissani⁷, Falko Böhringer⁸, Jens Kuhle⁹˒¹⁰, Anne-Katrin Pröbstel⁹˒¹¹˒¹², Xiao-Jun Ma², Péter Körtvelyessy⁴˒⁸˒¹³, Patrick Waters¹⁴, and Friedemann Paul¹˒³

¹ Experimental and Clinical Research Center (ECRC), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
² Alamar Biosciences, Fremont, California, USA
³ Neuroscience Clinical Research Center (NCRC), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
⁴ Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
⁵ Einstein Center Digital Future Berlin, Berlin, Germany
⁶ Division of Neurology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
⁷ Laboratory of Clinical and Experimental Neuroscience, Faculty of Medicine, Cadi Ayyad University, Marrakech, Morocco
⁸ Labor Berlin – Charité Vivantes Services GmbH, Berlin, Germany
⁹ Multiple Sclerosis Center and Research Centers for Clinical Neuroimmunology and Neuroscience (RC2NB) Neurology, University and University Hospital Basel, Basel, Switzerland
¹⁰ Department of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland
¹¹ Center for Neurology, Department of Neuroimmunology and Neuromuscular Diseases, University Hospital and University Bonn, Bonn, Germany
¹² German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
¹³ German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
¹⁴ Oxford Autoimmune Neurology Diagnostic Laboratory, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

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.