Abstract Details

Title Predictive Utility of Serum Protein Biomarkers from the Octave MSDA Panel for Optic Neuritis Events in People with Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S42 - Multiple Sclerosis: Biomarkers/Neuroimaging (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Background ON, a common manifestation in multiple sclerosis (MS), can substantially affect patients' quality of life. The prediction of ON using serum biomarkers could offer clinicians valuable insights into disease progression and potentially guide therapeutic strategies, however the efficacy of biomarkers in forecasting ON in MS remains underexplored.

Objective To assess the predictive power of serum protein biomarkers measured from the Octave Multiple Sclerosis Disease Activity (MSDA) immunoassay panel for predicting optic neuritis (ON) events in people with MS (pwMS) using machine learning models.

Design/Methods The proteomic analysis was performed in a subset of 109 patients from the larger CEG-MS initiative with ON prevalence of 50.5%. Patients either reported ON events 1.1(1.4) years after the baseline proteomic measurement or never reported ON events. Serum biomarker measurements from the Octave MSDA panel were extracted and pre-processed using proximity extension assay methodology on the Olink platform. Three machine learning models (Support-Vector-Machine, Logistic-Regression, and Linear-Discriminant-Analysis) were trained to predict ON from baseline biomarkers and demographics in a leave-one-out cross-validation approach to optimize the F1-score.

Results The top-performing model was constructed using a sequence of preprocessing with StandardScaler and feature selection, and a Linear-Discriminant-Analysis model with a validation F1-score of 0.67. The most influential features in the model were OPN, CXCL13, CXCL9, TNFSF13B, and age. Further inspection of the protein concentration changes suggested that elevations in the concentrations of OPN (p<0.05), CXCL13 (p<0.001), and CXCL9 (p<0.0001) were predictive of ON in the next 5 years.

Conclusions Multianalyte proteomic models that include key mediators in inflammatory processes are able to stratify pwMS regarding their risk of future ON occurrence. This suggests that heightened immune activation might precede and set the stage for the onset of clinical manifestations, offering a window of opportunity for early intervention.

Authors/Disclosures
Ferhan Qureshi (Octave Bioscience) PRESENTER	Mr. Qureshi has received personal compensation for serving as an employee of Octave Bioscience.
Kian Jalaleddini	No disclosure on file
Dejan Jakimovski, MD, PhD (Buffalo Neuroimaging Analysis Center, University at Buffalo)	Dr. Jakimovski has nothing to disclose.
Anisha Keshavan	No disclosure on file
Shannon McCurdy	No disclosure on file
Ati Ghoreyshi (Octave Bioscience)	No disclosure on file
Niels Bergsland (Buffalo Neuroimaging Analysis Center / State University of New York At Buffalo)	Prof. Bergsland has nothing to disclose.
Michael G. Dwyer III, MD, PhD (Buffalo Neurological Analysis Center)	Dr. Dwyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Keystone Heart, Ltd. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Dwyer has received research support from Novartis. The institution of Dr. Dwyer has received research support from Keystone Heart, Ltd. The institution of Dr. Dwyer has received research support from Bristol Myers Squibb. The institution of Dr. Dwyer has received research support from Roche.
Murali Ramanathan, PhD (University At Buffalo)	The institution of Dr. Ramanathan has received research support from DoD. Dr. Ramanathan has received publishing royalties from a publication relating to health care.
Bianca Weinstock-Guttman, MD (Department of Neurology, University At Buffalo)	Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme &Sanofi. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH.
Ralph H. Benedict, PhD (University At Buffalo)	Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Benedict has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Roche. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bristol Meyers Squibb. Dr. Benedict has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Benedict has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Brystal Mier Squibb. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Benedict has received research support from Genzyme. The institution of Dr. Benedict has received research support from Biogen. The institution of Dr. Benedict has received research support from Bristol Myer Squib. Dr. Benedict has received intellectual property interests from a discovery or technology relating to health care.
Robert Zivadinov, MD, PhD, FAAN (Buffalo Neuroimaging Analysis Center)	The institution of Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Filterlex. Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for 3D Communications. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Omnicuris. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurology Live. The institution of Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen.