Publication

Effects of Natalizumab on Circulating B Cells, T Regulatory Cells and Natural Killer Cells

Journal Paper/Review - May 5, 2010

Units
PubMed
Doi

Citation
Putzki N, Baranwal M, Tettenborn B, Limmroth V, Kreuzfelder E. Effects of Natalizumab on Circulating B Cells, T Regulatory Cells and Natural Killer Cells. Eur Neurol 2010; 63:311-317.
Type
Journal Paper/Review (English)
Journal
Eur Neurol 2010; 63
Publication Date
May 5, 2010
Issn Electronic
1421-9913
Pages
311-317
Brief description/objective

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.