Background: The monoclonal antibody natalizumab (NAT) inhibits the migration of lymphocytes throughout the\nbloodââ?¬â??brain barrier by blocking very late antigen (VLA)-4 interactions, thereby reducing inflammatory central\nnervous system (CNS) activity in patients with multiple sclerosis (MS). We evaluated the effects of different NAT\ntreatment regimens.\nMethods: We developed and optimised a NAT assay to measure free NAT, cell-bound NAT and VLA-4 expression\nlevels in blood and cerebrospinal fluid (CSF) of patients using standard and prolonged treatment intervals and after\nthe cessation of therapy.\nResults: In paired CSF and blood samples of NAT-treated MS patients, NAT concentrations in CSF were approximately\n100-fold lower than those in serum. Cell-bound NAT and mean VLA-4 expression levels in CSF were comparable\nwith those in blood. After the cessation of therapy, the kinetics of free NAT, cell-bound NAT and VLA-4 expression\nlevels differed. Prolonged intervals greater than 4 weeks between infusions caused a gradual reduction of free\nand cell-bound NAT concentrations. Sera from patients with and without NAT-neutralising antibodies could be\nidentified in a blinded assessment. The NAT-neutralising antibodies removed NAT from the cell surface in vivo\nand in vitro. Intercellular NAT exchange was detected in vitro.\nConclusions: Incorporating assays to measure free and cell-bound NAT into clinical practice can help to\ndetermine the optimal individual NAT dosing regimen for patients with MS
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