A study led by Samia J. Khoury, MD, BWH Department of Neurology, discovered that the drug natalizumab (NTZ) lowers plasmacytoid dendritic cell (PDC) frequency by 25 percent to 50 percent in the peripheral blood of patients with multiple sclerosis (MS). PDCs regulate the innate and adaptive immune responses by promoting antigen presentation and T cell activation.
NTZ is a humanized monoclonal antibody against the alpha-4 subunit of integrins, which are important structural proteins in the cell membrane including in PDCs. NTZ reduces the disease activity and severity of relapsing-remitting MS and has therefore been approved for use in patients. The researchers sought to determine the effect of NTZ treatment on the frequency of circulating dendritic cells, their activation, and subsequent induction of T cell differentiation or polarization in MS patients.
The study involved two cohorts of untreated, interferon-treated, and NTZ-treated MS patients for a total of 131 subjects. Treatment with NTZ induced a mature, activated phenotype in PDCs, with increased expression of the cell markers HLA-DR, TLR9, CCR7, IL-6 and IL-12. In contrast to the reduction in PDC frequency, myeloid dendritic cell (MDC) frequency in peripheral blood remained the same between NTZ-treated and untreated patients. However, PDC activation and subsequent T cell differentiation was not induced by NTZ treatment in in vitro experiments.
“The observed reduction in PDC frequency in blood may reflect a general decrease in central nervous system inflammation following NTZ treatment resulting in reduced PDC mobilization,” said Khoury.
The study was published online July 30, 2014 in PLOS ONE.