Lymphocyte Counts and Multiple Sclerosis Therapeutics: Between Mechanisms of Action and Treatment-Limiting Side Effects

Abstract

Although the detailed pathogenesis of multiple sclerosis (MS) is not completely understood, a broad range of disease-modifying therapies (DMTs) are available. A common side effect of nearly every MS therapeutic agent is lymphopenia, which can be both beneficial and, in some cases, treatment-limiting. A sound knowledge of the underlying mechanism of action of the selected agent is required in order to understand treatment-associated changes in white blood cell counts, as well as monitoring consequences. This review is a comprehensive summary of the currently available DMTs with regard to their effects on lymphocyte count. In the first part, we describe important general information about the role of lymphocytes in the course of MS and the essentials of lymphopenic states. In the second part, we introduce the different DMTs according to their underlying mechanism of action, summarizing recommendations for lymphocyte monitoring and definitions of lymphocyte thresholds for different therapeutic regimens.

Varicella-Zoster Reactivation in a Non-immunized Elderly Multiple Sclerosis Patient While on Delayed-Release Dimethyl Fumarate With Grade 2 Lymphopenia and Profoundly Low CD4+ and CD8+ Cell Counts: A Case Report

“…Zoster reactivation classically becomes more common with age (> 55 yrs), since advancing age reduces lymphopoiesis impairing cell-mediated immunity [4,6,7], with other factors being stress and smoking [4].…”

“…Zoster reactivation classically becomes more common with age (> 55 yrs), since advancing age reduces lymphopoiesis impairing cell-mediated immunity [ 4 , 6 , 7 ], with other factors being stress and smoking [ 4 ]. The patient had lower normal to grade 1 lymphopenia as her baseline and it might be because of her age admixed with DMF-induced lymphopenia raising plausibility of reduced lymphocytes, which otherwise could represent vigor of immunomodulation implying better disease control [ 1 ].…”

“…These are quite comprehensive in terms of screening recommendations, vaccination advice, the need for antibiotic prophylaxis, neuroimaging, laboratory checkups, medication dosing, and behavioral modifications [ 2 ]. Our case is not immunized with zoster vaccine and unfortunately, DMF has no proper structured guidelines regarding vaccination against OI prevention as other few DMTs have [ 2 ], although recommended monitoring regimes of lymphocyte threshold for individual DMTs are present [ 4 ] and perhaps any grade 2 lymphopenia may be reasonable to start monitoring for opportunistic infection [ 4 ]. We illustrate a tabular format of lymphocyte count vigilance and potential opportunistic pathogen mitigate plan while on DMTs (Table 2 ) [ 11 ].…”

“…Human immunodeficiency virus (HIV) itself is an important archetype as its association with PML is clearly seen when the CD4+ cell counts fall below 200 cells/µl [ 3 ]; likewise, CD8+ T cells are key in restraining John Cunningham virus (JC virus) where its decrement raises the possibility of viral CNS infection [ 1 ]. The use of DMTs in modulating or suppressing the immune system for MS management may risk the patient with lymphocytopenia raising the possibility of OI, yet this lymphopenia may contemplate as a biomarker for drug response, degree of immunomodulation [ 1 ], and drug compliance [ 4 ].…”

“…Anti-JC virus antibody index and changes on periodic MRI scans have been quite effective for risk identification and monitoring for PML while treating with natalizumab [ 5 ]. Other medications have surveillance programs too, to monitor the increased opportunistic infective risk and the appropriate action it demands [ 4 ]. The solicitude of reactivation of latent varicella-zoster virus infection in MS patients secondary to immune modulation is genuine [ 6 ].…”