Abstract
Natalizumab binds to α4 integrins expressed on lymphocytes and monocytes. It blocks the interaction of these integrins with their binding partners on vascular endothelial cells, and thereby prevents immune cells from entering inflamed tissues. Natalizumab is an effective treatment, but it carries the risk of progressive multifocal leukoencephalopathy (PML). Results reported in this issue of Neurology ® are relevant to both the beneficial and adverse effects of natalizumab.1 The authors investigated how natalizumab affects the T-cell receptor (TCR) repertoire of patients with multiple sclerosis (MS). Their main observations are that 1) the TCR repertoire seems to “normalize” during natalizumab treatment, that is, revert to the state observed in healthy subjects, and 2) the onset of PML and immune reconstitution inflammatory syndrome (IRIS) is accompanied or preceded by the appearance of distinct clonal T-cell expansions in blood or CSF.
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