Natalizumab effects on immune cell responses in multiple sclerosis.
OBJECTIVE
Our objective was to study in vivo biological effects of natalizumab on immune cell phenotype and function in multiple sclerosis (MS) patients.


METHODS
Blood was obtained before and after serial monthly natalizumab infusions to track functional expression of VLA-4 and migratory capacity of immune cells. The impact of infusion on activation thresholds of immune cells was evaluated.


RESULTS
Preinfusion VLA-4 expression differed across immune cell subsets. Natalizumab significantly, albeit partially, diminished VLA-4 expression on circulating immune cells. Cell subsets were differentially affected. Treatment significantly decreased migratory capacity of immune cells, correlating well with changes in VLA-4 expression. Effects of a single dose were not saturating and did not persist through the monthly dose interval. Infusion effect varied across patients but was remarkably stable in individual patients, over multiple infusions. Treatment significantly modulated proliferative responses of immune cells.


CONCLUSIONS
To our knowledge, we provide first proof of concept that natalizumab diminishes migratory capacity of immune cells. Our prospective study further shows that effects of therapy likely (1) differ for distinct immune cell subsets, (2) are not sustained over current dose interval, (3) have unique profiles in individual patients, and (4) include modulation of activation threshold of immune cells. Monitoring these parameters could be relevant to ongoing safety and efficacy considerations.
Niino
Masaaki
M
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada.
Bodner
Caroline
C
Simard
Marie-Lune
ML
Alatab
Sudabeh
S
Gano
Dawn
D
Kim
Ho Jin
HJ
Trigueiro
Manuela
M
Racicot
Denise
D
Guérette
Christine
C
Antel
Jack P
JP
Fournier
Alyson
A
Grand'Maison
Francois
F
Bar-Or
Amit
A
D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002465:Cell Movement / Q000187:drug effects; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D039441:Integrin alpha4 / Q000096:biosynthesis; D039041:Integrin alpha4beta1 / Q000096:biosynthesis / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000502:physiology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology*; D000069442:Natalizumab; D010641:Phenotype; D011446:Prospective Studies; D013268:Stimulation, Chemical
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D039041:Integrin alpha4beta1; D000069442:Natalizumab; D039441:Integrin alpha4