Differential effects of disease modifying drugs on peripheral blood B cell subsets: A cross sectional study in multiple sclerosis patients treated with interferon-β, 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-β (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 naïve 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-β treatments were associated with an increase in the fraction of naïve 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-β 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.

Déclaration de conflit d'intérêts

I have read the journal’s policy and the authors of this manuscript have the following competing interests: C.L. Kemmerer: reports no disclosures. V. Pernpeitner: reports no disclosures. C. Ruschil: reports no disclosures. A. Abdelhak: received research funding from the German multiple sclerosis society (DMSG) as well as travel grants from Teva and Novartis all not related to this work. M. Scholl: reports no disclosures. U. Ziemann: UZ has received honoraria from Biogen Idec GmbH, Bayer Vital GmbH, Bristol Myers Squibb GmbH, Pfizer, CorTec GmbH, Medtronic GmbH, and grants from European Research Council, German Research Foundation, German Ministry of Education and Research, Biogen Idec GmbH, Servier, and Janssen Pharmaceuticals NV, all not related to this work. M. Krumbholz: receives financial support from Sanofi-Genzyme, Merck, Novartis, Biogen, Celgene and Roche, not related to this study. B. Hemmer has served on scientific advisory boards for Novartis; he has served as DMSC member for AllergyCare and TG therapeutics; he or his institution have received speaker honoraria from Desitin; holds part of two patents; one for the detection of antibodies against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon. All conflicts are not relevant to the topic of the study. M.C. Kowarik: receives financial support from Merck, Sanofi-Genzyme, Novartis, Biogen, Celgene and Roche, not related to this study. The competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials.