Natalizumab alters T cell ratio in MS patients
Last Updated: 2006-11-17 15:25:23 -0400 (Reuters Health)

This may account for the development in some patients of progressive multifocal leukoencephalopathy (PML), a demyelinating disorder of the CNS caused by JC virus infection.

In the October issue of Neurology, Dr. Olaf Stuve of the VA North Texas Health Care System, Dallas and colleagues note that natalizumab (Tysabri) was voluntarily withdrawn from the market and its use was stopped in clinical trials after two patients with MS and one with Crohn’s disease developed PML. Subsequently, Tysabri has been made available again.

Natalizumab is a monoclonal antibody against the adhesion molecule, very late activation antigen 4, which is an alpha-4-beta-1 integrin.

The team examined CSF and peripheral blood specimens from MS patients who had undergone natalizumab therapy and found that CSF levels of CD4+ to CD8+ were similar to those seen in HIV patients. Ratios normalized within 6 months of cessation of natalizumab therapy.

The ratios in peripheral blood progressively decreased with the number of natalizumab doses but remained within normal levels.

The researchers suggest that lower expression of unbound alpha4 integrin on CD4+ T cells may be a mechanism underlying the altered T-cell ratios.

"Although the mechanism remains undefined at present, the implications for immune control of CNS infections are potentially important," the researchers say, "and suggest that prolonged, uninterrupted natalizumab therapy may eventually alter systemic immune responses."

In an accompanying editorial, Drs. Henry F. McFarland and Steven Jacobsen of the National Institutes of Health, Bethesda, Maryland note that "careful biological monitoring" will be required as patients return to treatment with natalizumab.

The results, they conclude, "have implications for not only natalizumab but also other therapies that have similar mechanisms."

Arch Neurol 2006;63:1383-1387