B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients

Amy E. Lovett-Racke, Matthew Gormley, Yue Liu, Yuhong Yang, Calsey Graham, Sibyl Wray, Michael K. Racke, Richard Shubin, Cary Twyman, Enrique Alvarez, Ann Bass, James L. Eubanks, Edward Fox

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Multiple sclerosis (MS)is a demyelinating disease of the central nervous system, thought to be mediated by myelin-specific CD4+ T cells. However, B cell depletion has proven to be an effective therapy for MS, but the mechanism is not well understood. This study was designed to determine how B cell depletion changes lymphocyte profiles. During a phase IIa clinical trial with ublituximab, a novel CD20 antibody, blood was collected from 48 MS patients at 11 time points over 24 weeks and the lymphocyte profiles were analyzed by flow cytometry. The percentage of naïve CD4+ and CD8+ T cells increased, while the percentage of both effector and central memory T cells declined. CD4+ Th1 effector cells decreased, while there was a significant increase in CD4+ regulatory T cells. The depletion of B cells had a favorable shift in the lymphocyte landscape, reducing the number of naïve T cells becoming activated and transitioning to memory T cells. The ratio of Th1 cells to CD4+ regulatory T cells declined, suggesting that immune regulation was being restored. These data suggest that loss of B cells as antigen presenting cells is a major mechanism of action for the beneficial effects of CD20 antibody therapy in MS.

Original languageEnglish (US)
Pages (from-to)187-197
Number of pages11
JournalJournal of Neuroimmunology
Volume332
DOIs
StatePublished - Jul 15 2019

Fingerprint

Multiple Sclerosis
B-Lymphocytes
T-Lymphocytes
Th1 Cells
Regulatory T-Lymphocytes
Lymphocytes
Lymphocyte Depletion
Antibodies
Demyelinating Diseases
Antigen-Presenting Cells
Myelin Sheath
Flow Cytometry
Central Nervous System
Clinical Trials
Therapeutics

Keywords

  • B cell
  • CD20
  • Multiple sclerosis
  • Regulatory T cell
  • T cell
  • Ublituximab

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Cite this

B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients. / Lovett-Racke, Amy E.; Gormley, Matthew; Liu, Yue; Yang, Yuhong; Graham, Calsey; Wray, Sibyl; Racke, Michael K.; Shubin, Richard; Twyman, Cary; Alvarez, Enrique; Bass, Ann; Eubanks, James L.; Fox, Edward.

In: Journal of Neuroimmunology, Vol. 332, 15.07.2019, p. 187-197.

Research output: Contribution to journalArticle

Lovett-Racke, AE, Gormley, M, Liu, Y, Yang, Y, Graham, C, Wray, S, Racke, MK, Shubin, R, Twyman, C, Alvarez, E, Bass, A, Eubanks, JL & Fox, E 2019, 'B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients', Journal of Neuroimmunology, vol. 332, pp. 187-197. https://doi.org/10.1016/j.jneuroim.2019.04.017
Lovett-Racke, Amy E. ; Gormley, Matthew ; Liu, Yue ; Yang, Yuhong ; Graham, Calsey ; Wray, Sibyl ; Racke, Michael K. ; Shubin, Richard ; Twyman, Cary ; Alvarez, Enrique ; Bass, Ann ; Eubanks, James L. ; Fox, Edward. / B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients. In: Journal of Neuroimmunology. 2019 ; Vol. 332. pp. 187-197.
@article{be636e38995743fc87d86246f37442cc,
title = "B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients",
abstract = "Multiple sclerosis (MS)is a demyelinating disease of the central nervous system, thought to be mediated by myelin-specific CD4+ T cells. However, B cell depletion has proven to be an effective therapy for MS, but the mechanism is not well understood. This study was designed to determine how B cell depletion changes lymphocyte profiles. During a phase IIa clinical trial with ublituximab, a novel CD20 antibody, blood was collected from 48 MS patients at 11 time points over 24 weeks and the lymphocyte profiles were analyzed by flow cytometry. The percentage of na{\"i}ve CD4+ and CD8+ T cells increased, while the percentage of both effector and central memory T cells declined. CD4+ Th1 effector cells decreased, while there was a significant increase in CD4+ regulatory T cells. The depletion of B cells had a favorable shift in the lymphocyte landscape, reducing the number of na{\"i}ve T cells becoming activated and transitioning to memory T cells. The ratio of Th1 cells to CD4+ regulatory T cells declined, suggesting that immune regulation was being restored. These data suggest that loss of B cells as antigen presenting cells is a major mechanism of action for the beneficial effects of CD20 antibody therapy in MS.",
keywords = "B cell, CD20, Multiple sclerosis, Regulatory T cell, T cell, Ublituximab",
author = "Lovett-Racke, {Amy E.} and Matthew Gormley and Yue Liu and Yuhong Yang and Calsey Graham and Sibyl Wray and Racke, {Michael K.} and Richard Shubin and Cary Twyman and Enrique Alvarez and Ann Bass and Eubanks, {James L.} and Edward Fox",
year = "2019",
month = "7",
day = "15",
doi = "10.1016/j.jneuroim.2019.04.017",
language = "English (US)",
volume = "332",
pages = "187--197",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
publisher = "Elsevier",

}

TY - JOUR

T1 - B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients

AU - Lovett-Racke, Amy E.

AU - Gormley, Matthew

AU - Liu, Yue

AU - Yang, Yuhong

AU - Graham, Calsey

AU - Wray, Sibyl

AU - Racke, Michael K.

AU - Shubin, Richard

AU - Twyman, Cary

AU - Alvarez, Enrique

AU - Bass, Ann

AU - Eubanks, James L.

AU - Fox, Edward

PY - 2019/7/15

Y1 - 2019/7/15

N2 - Multiple sclerosis (MS)is a demyelinating disease of the central nervous system, thought to be mediated by myelin-specific CD4+ T cells. However, B cell depletion has proven to be an effective therapy for MS, but the mechanism is not well understood. This study was designed to determine how B cell depletion changes lymphocyte profiles. During a phase IIa clinical trial with ublituximab, a novel CD20 antibody, blood was collected from 48 MS patients at 11 time points over 24 weeks and the lymphocyte profiles were analyzed by flow cytometry. The percentage of naïve CD4+ and CD8+ T cells increased, while the percentage of both effector and central memory T cells declined. CD4+ Th1 effector cells decreased, while there was a significant increase in CD4+ regulatory T cells. The depletion of B cells had a favorable shift in the lymphocyte landscape, reducing the number of naïve T cells becoming activated and transitioning to memory T cells. The ratio of Th1 cells to CD4+ regulatory T cells declined, suggesting that immune regulation was being restored. These data suggest that loss of B cells as antigen presenting cells is a major mechanism of action for the beneficial effects of CD20 antibody therapy in MS.

AB - Multiple sclerosis (MS)is a demyelinating disease of the central nervous system, thought to be mediated by myelin-specific CD4+ T cells. However, B cell depletion has proven to be an effective therapy for MS, but the mechanism is not well understood. This study was designed to determine how B cell depletion changes lymphocyte profiles. During a phase IIa clinical trial with ublituximab, a novel CD20 antibody, blood was collected from 48 MS patients at 11 time points over 24 weeks and the lymphocyte profiles were analyzed by flow cytometry. The percentage of naïve CD4+ and CD8+ T cells increased, while the percentage of both effector and central memory T cells declined. CD4+ Th1 effector cells decreased, while there was a significant increase in CD4+ regulatory T cells. The depletion of B cells had a favorable shift in the lymphocyte landscape, reducing the number of naïve T cells becoming activated and transitioning to memory T cells. The ratio of Th1 cells to CD4+ regulatory T cells declined, suggesting that immune regulation was being restored. These data suggest that loss of B cells as antigen presenting cells is a major mechanism of action for the beneficial effects of CD20 antibody therapy in MS.

KW - B cell

KW - CD20

KW - Multiple sclerosis

KW - Regulatory T cell

KW - T cell

KW - Ublituximab

UR - http://www.scopus.com/inward/record.url?scp=85065146823&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065146823&partnerID=8YFLogxK

U2 - 10.1016/j.jneuroim.2019.04.017

DO - 10.1016/j.jneuroim.2019.04.017

M3 - Article

C2 - 31077854

AN - SCOPUS:85065146823

VL - 332

SP - 187

EP - 197

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

ER -