Flow cytometry and drug-monitoring of natalizumab saturation of immune cells in multiple sclerosis

Background: Natalizumab (Tysabri) is a blocking antibody specific to the α-4 integrin subunit and can be detected on the surface of immune cells by flow cytometry. We investigated if the determination of natalizumab saturation of immune cells has the potential to act as a biomarker for treatment effectiveness in multiple sclerosis (MS). Methods: Natalizumab saturation of immune cells from 11 patients was measured before the start of treatment and after 4, 8, and 12 weeks of natalizumab therapy on T cells (CD3+) and T cell subsets [naive (CD45RA+/memory (CD45R0+) CD4+ and CD8+] by flow cytometry. Results: At weeks 4, 8, and 12 the average (n=9) natalizumab saturation of T cells approximated 80%. One patient with natalizumab neutralizing antibodies (NABs) and another patient with irregular infusion intervals were identified by abnormalities in the natalizumab saturation of cells. Different α-4 expression levels of T cell subpopulations were irrelevant to measuring cellular natalizumab saturation. Conclusions: We showed that monitoring natalizumab saturation of T cells by flow cytometry is a useful and routine-qualified method to identify patients with a reduced treatment effect due to NABs or irregular infusion intervals. Further studies to determine a cut-off value for suboptimal natalizumab saturation of immune cells will also show the potential of this parameter concerning more individualized treatment schedules. Considering the risk of opportunistic infections it is very important to increase the safety of this highly effective MS therapy.