Natalizumab Affects T-Cell Phenotype in Multiple Sclerosis: Implications for JCV Reactivation

Area of Science:

• Immunology
• Neuroscience
• Virology

Background:

• Natalizumab is an effective therapy for relapsing-remitting multiple sclerosis (RRMS).
• Therapeutic efficacy is limited by John Cunningham polyomavirus (JCV) reactivation and progressive multifocal leukoencephalopathy (PML) development.
• Understanding natalizumab's effects on T-lymphocytes is crucial for managing PML risk.

Purpose of the Study:

• To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation.
• To investigate the impact of natalizumab on CD49d expression and T-lymphocyte subsets in RRMS patients.
• To elucidate the mechanisms underlying PML development in natalizumab-treated patients.

Main Methods:

• Longitudinal assessment of CD49d expression, T-lymphocyte subsets (CD4+, CD8+), JCV-specific antibodies, and JCV-DNA in 26 natalizumab-treated RRMS patients.
• Statistical analyses using GraphPad Prism and R.
• Monitoring of peripheral blood and urine for JCV-DNA and serum for JCV antibodies.

Main Results:

• Natalizumab treatment reduced CD49d expression on memory and effector T-lymphocytes.
• Accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months.
• Increased CD4+ and CD8+ T-lymphocyte immune-activation occurred after 24 months.
• Higher percentages of CD8+ effectors correlated with detectable JCV-DNA.

Conclusions:

• Natalizumab reduces CD49d expression on CD8+ T-lymphocytes, limiting CNS migration and causing peripheral accumulation.
• Impaired central nervous system immune surveillance and JCV reactivation contribute to PML risk in natalizumab-treated RRMS patients.
• These findings highlight the importance of monitoring T-lymphocyte profiles and JCV status during natalizumab therapy.