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 journalArticlepeer-review

9 Scopus citations

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

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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