Novel mechanisms of immune modulation of natalizumab in multiple sclerosis patients.

The goal of this study was to investigate the effects of natalizumab therapy on the immune cell composition and phenotype in the blood of relapsing MS patients treated over the course of 12 months. We collected peripheral blood from 26 RRMS patients before treatment onset, and then 6 and 12 months after therapy. PBMC was isolated and then analyzed for phenotypic characteristics by FACS and for cytokine production by ELISA. The results of our studies showed changes in both numbers and activation states of immune cells following therapy. These changes were observed at the 6 month timepoint and generally persisted through the 12 month timepoint. The proportions of NK cells (CD3⁻CD56+) and hematopoetic stem cells (CD34+lin⁻) were increased after natalizumab treatment. Decreases were noted in numbers of CD14+ monocytes, and possibly their migratory potential, since their expression levels of α4β1 were decreased. Relative numbers of CD20+ B cells were increased, but the proportion of CD20+ cells expressing high levels of α4β1 integrin was decreased. While proportions of CD4+ and CD8+ T cells did not change, the percentage of cells expressing α4β1 integrin was significantly decreased for both subsets. Natalizumab therapy produces a number of phenotypic changes in the immune composition of peripheral blood. These changes may help to explain both the mechanisms of action of natalizumab and also shed light on the potential for the observed increase in PML in these patients.