01 Set Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation
The anti-CD49d monoclonal antibody natalizumab is an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML).
Aim of the study was to correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation in RRMS patients.
JCV-specific antibodies (serum), JCV-DNA (blood, urine), CD49d expression and peripheral blood T-lymphocyte subset counts were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R.
Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA.
Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects.