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. 2023 Oct;29(11-12):1465-1470.
doi: 10.1177/13524585231189641. Epub 2023 Aug 12.

High CD4+:CD8+ ratios with herpes zoster infections in patients with multiple sclerosis on dimethyl fumarate

Alexandra Balshi  1 , Emma Saart  1   2 , Sarbesh Pandeya  1 , John Dempsey  1 , Ursela Baber  1 , Jacob A Sloane  3
Affiliations

High CD4+:CD8+ ratios with herpes zoster infections in patients with multiple sclerosis on dimethyl fumarate

Alexandra Balshi et al. Mult Scler. 2023 Oct.

Abstract

Background: Dimethyl fumarate (DMF) depletes CD8+ and CD4+ T cells, and cases of herpes zoster (HZ) in patients with multiple sclerosis (MS) on DMF have been documented.

Objectives: To evaluate lymphocyte subsets in patients with MS who developed HZ on DMF (Tecfidera) compared to matched controls who did not develop HZ.

Methods: We used linear mixed-effects models to test for differences in white blood cell count, lymphocyte percentage, absolute lymphocyte count, CD3+ percentage, absolute CD3+ count, CD4+ percentage, absolute CD4+ count, CD8+ percentage, absolute CD8+ count, and CD4+:CD8+ ratio over time in HZ and non-HZ groups.

Results: Eighteen patients developed HZ while on DMF. The linear mixed-effects model for CD4+:CD8+ ratio showed a significant difference between the HZ and non-HZ groups (p = 0.033). CD4+:CD8+ ratio decreased over time in the HZ group and increased over time in the non-HZ group.

Conclusion: Patients with MS who develop HZ while on DMF have high CD4+:CD8+ ratios, suggesting an imbalance of CD4+ and CD8+ cells that may put a patient at risk for developing HZ while on DMF. This result emphasizes the need for lymphocyte subset monitoring (including CD4+:CD8+ ratios) on DMF, as well as vaccination prior to DMF initiation.

Keywords: Dimethyl fumarate; disease-modifying therapies; immunology; multiple sclerosis.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.A.S. has grant funding from the National MS Society and has consulted for Biogen, Genentech, Teva, Banner, Sanofi, and Cellgene. The remaining authors have no conflicts to declare.

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