Tysabri’s Success in Impairing the Immune System in RRMS May Be Source of Its Problems

Inês Martins, PhD avatar

by Inês Martins, PhD |

Share this article:

Share article via email
T cells and MS

Although Tysabri (natalizumab) is a highly effective in treating patients with relapsing-remitting multiple sclerosis (RRMS), some may develop progressive multifocal leukoencephalopathy (PML). According to a new study, this occurs because Tysabri impairs immune surveillance in the central nervous system and reactivates the latent John Cunningham polyomavirus (JCV).

The study, “Natalizumab Affects T-Cell Phenotype in Multiple Sclerosis: Implications for JCV Reactivation,” published in the journal PLOS One, was developed by researchers at Sapienza University in Italy.

Tysabri, an anti-CD49d humanized monoclonal antibody, is known to impair the migration of inflammatory cells into the central nervous system (CNS), leading to a significant decrease in relapses in RRMS patients. It is currently one of the most effective therapies against RRMS, but reactivation of JCV — with consequent development of PML — often limits its use.

Currently, standard of care for RRMS patients includes the routine measurement of anti-JCV antibodies in the serum to assess patients’ risk of developing PML. But some patients have JCV infections even without detectable antibody responses, suggesting that additional markers are required to better risk-stratify patients for PML.

Previous studies have reported that Tysabri modifies the number of certain immune cells in circulation, and decreases CD49d expression at the surface of the immune cells. Therefore, the researchers aimed to assess CD49d expression and alterations in circulating immune cells in a long-term setting that could correlate with JCV reactivation.

They enrolled 26 RRMS patients, who were evaluated before the first Tysabri infusion, and again at 12 and 24 months post-treatment. Results revealed that Tysabri treatment reduced CD49d expression in several types of T-cells, which led to their accumulation in the blood.

The researchers hypothesized that an increase in those specific subsets of cells in the blood corresponded to a decrease in the CNS, suggesting that immune surveillance mechanisms of the CNS may be compromised in Tysabri-treated patients.

In addition, they found that Tysabri could activate and mobilize JCV-infected cells from latency sites, inducing systemic JCV spread.

Investigators believe that monitoring CD49d expression in MS patients may be useful in understanding potential JCV reactivation in patients under Tysabri treatment.

Dancing Doodle

Did you know some of the news and columns on Multiple Sclerosis News Today are recorded and available for listening on SoundCloud? These audio news stories give our readers an alternative option for accessing information important for them.

Listen Here