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Natalizumab differentially affects plasmablasts and B cells in multiple sclerosis.

Alexander Cuculiza Henriksen1, Cecilie Ammitzbøll1, Eva Rosa Petersen1

  • 1Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Glostrup, Denmark.

Multiple Sclerosis and Related Disorders
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Summary

Natalizumab treatment increases B cells but decreases plasmablasts and IgG in multiple sclerosis (MS) patients. Plasmablasts, which express CD49d, are absent in cerebrospinal fluid after treatment.

Keywords:
B cellsFlow cytometryMultiple sclerosisNatalizumabPlasmablasts

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Area of Science:

  • Immunology
  • Neuroscience
  • Pharmacology

Background:

  • Natalizumab therapy for multiple sclerosis (MS) alters B cell dynamics and immunoglobulin G (IgG) levels.
  • Plasmablasts are key IgG producers, and their development is linked to CD49d expression.

Purpose of the Study:

  • To investigate the effect of natalizumab on plasmablast development in MS patients.
  • To analyze CD49d expression on B cell subsets and its relation to plasmablasts.

Main Methods:

  • Retrospective analysis of B cell subsets in MS patients treated with natalizumab using flow cytometry.
  • Quantification of CD49d expression on B cells in healthy controls and MS patients.
  • Comparison of B cell subsets in blood and cerebrospinal fluid (CSF) between treated and untreated MS patients.

Main Results:

  • Natalizumab increased B cell frequency and counts, particularly memory B cells, but decreased plasmablast frequency and IgG levels.
  • Plasmablasts exhibited high CD49d expression and were undetectable in the CSF of natalizumab-treated patients.
  • Reduced memory B cell counts in unstable treated patients suggest potential central nervous system (CNS) recruitment.

Conclusions:

  • Natalizumab increases circulating B cells and decreases IgG, while reducing plasmablast frequency and eliminating them from CSF.
  • High CD49d expression on plasmablasts may influence their trafficking.
  • Decreased memory B cells in unstable patients warrants further investigation into CNS recruitment.