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

PLoS One. 2020 Jul 27;15(7):e0235449. doi: 10.1371/journal.pone.0235449. eCollection 2020.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / classification
  • Antigens, CD / immunology
  • Antigens, CD19
  • B-Lymphocyte Subsets / classification
  • B-Lymphocyte Subsets / drug effects*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Cross-Sectional Studies
  • Dimethyl Fumarate / administration & dosage
  • Female
  • Fingolimod Hydrochloride / administration & dosage
  • Flow Cytometry
  • Glatiramer Acetate / administration & dosage
  • Humans
  • Immunologic Memory / drug effects*
  • Immunologic Memory / immunology
  • Immunophenotyping
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / immunology
  • Interferon-beta / administration & dosage
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • Natalizumab / administration & dosage
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, CD19
  • Immunosuppressive Agents
  • Natalizumab
  • Glatiramer Acetate
  • Interferon-beta
  • Dimethyl Fumarate
  • Fingolimod Hydrochloride

Grants and funding

The Munich Cluster for Systems Neurology (SyNergy), Munich, Germany is a non-commercial funding program which provided support in the form of salary and research materials for M.C. Kowarik, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding of B. Hemmer by SyNergy was not related to this study. The specific roles of the authors are articulated in the ‘author contributions’ section.