Abstract Details

Title CD4 T Cell Responses to the Epstein-Barr Virus are Reduced by Disease-modifying Therapies in Patients with Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (8:00 AM-9:00 AM)

Poster/Presentation
Number 1-014

Objective

To investigate the impact of disease-modifying therapies (DMTs) on CD4 T cell responses to Epstein-Barr virus (EBV) antigens in patients with multiple sclerosis (MS).

Background

EBV infection is strongly associated with MS risk. DMTs are effective in treating MS and have been demonstrated to reduce CD8 T cell responses to EBV - particularly anti-CD20, teriflunomide and dimethyl fumarate. However, their effect on CD4 T cell responses to EBV remains less clear, despite the potential importance of these cells in MS immunopathology.

Design/Methods We conducted a cross-sectional study of 60 relapsing-remitting MS patients: 23 treatment-naïve and 37 on various DMTs (22 anti-CD20, 8 natalizumab, 4 dimethyl fumarate, 3 others). CD4 T cell responses to EBV latent and lytic antigens were assessed separately using IFN-γ ELISPOT assays, measuring the number of spot-forming cells (SFCs).

Results Treatment-naïve MS patients showed a predominant CD4 T cell response to EBV lytic antigens, with 10-fold higher median SFCs compared to latent antigens (p<0.001). DMT-treated MS patients, especially those on anti-CD20 therapies, exhibited significantly reduced responses to lytic antigens. The anti-CD20 group showed a 75% decrease in median SFCs for lytic antigens (p<0.001), while responses to latent antigens remained unchanged. Other DMTs also reduced EBV antigen responses, similar to anti-CD20 therapies. Notably, natalizumab was the exception, showing no significant reduction in responses to latent or lytic EBV antigens.

Conclusions

DMTs, particularly anti-CD20 therapies, significantly reduce CD4 T cell responses to EBV lytic antigens in MS patients, while responses to latent antigens remain largely unchanged. This specific effect on lytic antigen responses may contribute to the therapeutic efficacy of these treatments, possibly by reducing EBV-driven CD4 T cell help to myelin-targeting CD8 T cells. Our findings shed light on how DMTs affect EBV-specific immune responses in MS, pointing to possible new treatment approaches targeting EBV lytic antigen presentation.

Authors/Disclosures
Natalia Drosu PRESENTER	Ms. Drosu has nothing to disclose.
Philippe-Antoine Bilodeau, MD (Massachusetts General Hospital)	Dr. Bilodeau has nothing to disclose.
Joao Vitor Mahler, MD	Dr. Mahler has received research support from The Sumaira Foundation.
Monique Anderson, MD, PhD (Mass General Hospital)	Dr. Anderson has nothing to disclose.
Takahisa Mikami, MD (Massachusetts General Hospital)	Dr. Mikami has nothing to disclose.
Natasha Bobrowski-Khoury, PhD (Mass General Hospital/Harvard Medical School)	Dr. Bobrowski-Khoury has nothing to disclose.
Michael Levy, MD, PhD, FAAN (Massachusetts General Hospital/Harvard Medical School)	Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Levy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various law firms. The institution of Dr. Levy has received research support from National Institutes Health.

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