Differential Effects Of Disease Modifying Drugs On Peripheral Blood B Cell Subsets: A Cross Sectional Study In Multiple Sclerosis Patients Treated With Interferon-Beta, Glatiramer Acetate, Dimethyl Fumarate, Fingolimod Or Natalizumab

Background Several disease modifying drugs (DMDs) have been approved for the treatment of multiple sclerosis (MS), however, little is known about their differential impact on peripheral blood (PB) B cell subsets. Methods We performed a cross sectional study on PB B cells in MS patients treated with interferon-beta (n = 25), glatiramer acetate (n = 19), dimethyl fumarate (n = 15), fingolimod (n = 16) or natalizumab (n = 22), untreated MS patients (n = 20), and in patients with non-inflammatory neurological diseases (n = 12). Besides analyzing routine laboratory data, flow cytometry was performed to analyze naive B cells (CD19+CD20+CD27-IgD+), non-class switched (CD19+CD20+CD27+IgD+) and class-switched memory B cells (CD19+CD20+CD27+IgD-), double negative B cells (CD19+CD20lowCD27-IgD-) and plasmablasts (CD19+CD20lowCD27+CD38++). Results Treatment associated changes were found for the overall B cell pool as well as for all B cell subsets. Natalizumab increased absolute numbers and percentage of all B cells mainly by expanding the memory B cell pool. Fingolimod decreased absolute numbers of all B cell subsets and the percentage of total B cells. Fingolimod, dimethyl fumarate and interferon-beta treatments were associated with an increase in the fraction of naive B cells while class switched and non-class switched memory B cells showed decreased percentages. Conclusion Our results highlight differential effects of DMDs on the PB B cell compartment. Across the examined treatments, a decreased percentage of memory B cells was found in dimethyl fumarate, interferon-beta and fingolimod treated patients which might contribute to the drugs' mode of action in MS. Further studies are necessary to decipher the exact role of B cell subsets during MS pathogenesis.