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Updated: Jun 13, 2026
Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
Effects of natalizumab on circulating B cells, T regulatory cells and natural killer cells
Norman Putzki1, Manoj Kumar Baranwal, Barbara Tettenborn
1Department of Neurology, University Clinic Essen, University of Duisburg-Essen, Essen, Germany. norman.putzki @ kssg.ch
Background:
Natalizumab is a humanized monoclonal antibody directed against very late activation antigen 4 (VLA-4) and has a potent effect on disease activity in multiple sclerosis. Blockade of VLA-4 with natalizumab may not only interfere with autoimmunological mechanisms but also with central nervous system immune surveillance.
Methods:
Longitudinal ex vivo and in vitro study to determine the effect of natalizumab on the frequency of distinct immune cells and on the frequency and suppressive function of natural CD4+CD25+ regulatory T cells (Tregs).
Results:
Natalizumab binding to VLA-4 was more marked for B cells than for T cells (49% reduction in VLA-4-expressing B cells compared to 24.5% reduction of T cells). There was an increase in circulating B cells over T cells (2.6 vs. 1.5 fold, p < 0.001). Natural killer cells increased 1.5-fold (p = 0.01). Natalizumab led to a relative decrease in CD4+CD25+ Tregs from 18.9 to 14.1% (p = 0.04). The impaired suppressive capacity of Tregs was not restored.
Conclusion:
Natalizumab reduces VLA-4 expression on all investigated immune cells, but changes were most marked for B cells. Further differential effects on immune cells may be relevant to opportunistic central nervous system infections during treatment with natalizumab.
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