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Natalizumab (NTZ) is a recombinant humanised immunoglobulin G4 monoclonal antibody that selectively inhibits adhesion of α4-β1 receptor on the surface of lymphocytes and hinders circulating cells from leaving the vascular compartment of the brain.1 NTZ is associated with a risk of developing progressive multifocal leukoencephalopathy (PML), estimated at approximately 1/200 in JCV-positive patients after 24 months treatment duration.1 The overall survival rate is 71% in PML secondary to NTZ treatment, which is substantially better than the often-fatal course of PML in other immunosuppressed patients.2 This reflects the fact that immune reconstitution is more easily obtained in NTZ patient by treatment cessation.3 Immune reconstitution inflammatory syndrome (IRIS), characterised by contrast-enhancing MRI lesions with clinical deterioration, is observed in almost all PML patients after NTZ cessation.2 Plasma exchange (PLEX) is usually initiated after NTZ cessation to remove remaining circulating NTZ levels, which favours the immune reconstitution, whereas intravenous corticosteroids (CS) are given to suppress IRIS development.1 Nevertheless, the increased peripheral functional T-cell expansion following PLEX can be seen as an accelerator for IRIS, and the negative impact of CS on JCV-specific CD8 T cell response is also at risk of inhibiting the physiological immune response against the JC virus (JCV).
Report of a case
A patient was diagnosed with relapsing-remitting MS at the age of 46 years. Her JCV IgG serum status was positive 6 months after NTZ treatment initiation. After 22 infusions, she presented …
Contributors PHL and SH: study concept and design; acquisition of data; drafting of the manuscript; administrative, technical and material support; study supervision. PHL, CB, RIF, LK, RDP, FB and SH: analysis and interpretation of data; critical revision of the manuscript for important intellectual content.
Funding PHL is supported by the Swiss National Foundation and the Swiss Multiple Sclerosis Society.
Competing interests PHL has received honoraria for speaking from Biogen-Idec, Geneuro, Merck Serono, Novartis, Sanofi-Aventis, Teva; consulting fees from Biogen-Idec, Geneuro, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva; research grants from Biogen-Idec, Merck Serono, Novartis.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.