Effects of natalizumab on circulating B cells, T regulatory cells and natural killer cells.
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.


CONCLUSIONS
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.
Putzki
Norman
N
Department of Neurology, University Clinic Essen, University of Duisburg-Essen, Essen, Germany. norman.putzki @ kssg.ch
Baranwal
Manoj Kumar
MK
Tettenborn
Barbara
B
Limmroth
Volker
V
Kreuzfelder
Ernst
E
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D066298:In Vitro Techniques; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D000069442:Natalizumab; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015704:CD4 Antigens; D016827:CD8 Antigens; C508017:IL2RA protein, human; D007155:Immunologic Factors; D039041:Integrin alpha4beta1; D053645:Interleukin-2 Receptor alpha Subunit; D000069442:Natalizumab