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Natalizumab effects on immune cell responses in multiple sclerosis
Author(s) -
Niino Masaaki,
Bodner Caroline,
Simard MarieLune,
Alatab Sudabeh,
Gano Dawn,
Kim Ho Jin,
Trigueiro Manuela,
Racicot Denise,
Guérette Christine,
Antel Jack P.,
Fournier Alyson,
Grand'Maison Francois,
BarOr Amit
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20859
Subject(s) - natalizumab , immune system , multiple sclerosis , immunology , cell , medicine , biology , genetics
Abstract 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. Interpretation 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. Ann Neurol 2006;59:748–754