This study from Sweden looked at the changes in the T-cell receptor (TCR) repertoire in both CSF and peripheral blood in people with MS treated with natalizumab for at least 18 months. It included five cases of natalizumab-associated PML with age-matched people with MS not treated with natalizumab and healthy controls.
The researchers found that people with MS presented with peripheral TCR repertoire expansions in blood, which was less prominent during treatment with natalizumab. While in the CSF, TCR restrictions were most pronounced in people with MS treated with natalizumab. In the longitudinal samples obtained from those who developed PML, new identical TCR receptor length expansions in blood and CSF were seen following plasma exchange and preceded the development of immune reconstitution inflammatory syndrome (IRIS). Overall, this demonstrates significant TCR repertoire restrictions in CSF of patients treated with natalizumab, reflecting a likely altered immune surveillance of the central nervous system. There appears to be an impaired peripheral expansion of antigen-specific T cells. Following plasma exchange, the increased reconstitution of peripheral T-cell expansion may trigger PML-IRIS. These results suggest that natalizumab causes broader changes in the T-cell immune response beyond lymphocyte migration.
Authors: Warnke C, Mausberg AK
Source: Neurology. 2013 Sep 18. [Epub ahead of print]
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