2021 CMSC Annual Meeting

Combinatorial Analysis of Plasma and DNA Methylation Biomarkers in African American Patients with Multiple Sclerosis

NIB03

Background:
African American patients are at increased risk of developing severe forms of multiple sclerosis and have been underrepresented in clinical research studies. Many of these patients have a sub-optimal response to disease modifying therapies. To address this need, we have established the UIC Neuroimmunology Biobank.
Objectives:
Here our goal was to characterize plasma biomarkers in MS patients and control donors and perform combinatorial analysis with whole blood methylomics.
Methods:
Plasma biospecimens (n=53 MS; n=30 controls) were from the UIC Neuroimmunology Biobank. Approximately 55% of the donors identify as Black or African American. Disease modifying treatments were used in 98% of MS donors and included dimethyl fumarate (38%), ocrelizumab (23%), glatiramer acetate (17%), and natalizumab (11%). Four plasma biomarkers were assessed using the Quanterix ultrasensitive Simoa assay: neurofilament light (NFL), tau, glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCHL). In a subset of 46 donors, Infinium MethylationEPIC beadarrays were utilized to characterize genomic DNA methylation. Acquisition and analysis of data were performed at the Carver Biotechnology Center at the University of Illinois, Urbana. Data were analyzed using multiple statistical packages in R software.
Results:
Increased plasma NFL levels were observed for African Americans with MS as compared to white MS patients. Further analysis of plasma NFL was performed following adjustments for age and technical variation. Age adjusted plasma NFL showed a statistically significant increase in younger African American MS patients (40 yrs of age or younger) as compared to age-matched African American controls. Combined analysis with whole blood methylomics revealed distinct associations between DNA methylation and age adjusted NFL in MS patients as compared to controls.
Conclusions:
African American patients with MS demonstrate higher plasma NFL concentrations as compared to white MS patients. Younger African American MS patients have higher age-adjusted NFL levels as compared to age-matched controls. In addition, different patterns of DNA methylation in peripheral immune cells were observed in MS patients and control donors with elevated NFL values. These results suggest distinct mechanisms of neuronal injury in African American patients with MS.
This work was supported by funding from Biogen.