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Objectives: Dendritic cells (DCs) serve a critical role both in promoting and inhibiting adaptive immunity. The goal of this study was to investigate the effect of natalizumab (NTZ) treatment on DC numbers, phenotype, and function in patients with multiple sclerosis (MS)., Methods: Frequency and phenotype of myeloid and plasmacytoid DCs (MDCs and PDCs, respectively) were analyzed in blood from two separate cohorts of untreated, interferon-treated, or NTZ-treated MS patients. In addition, PDCs were stimulated with CpG-containing oligonucleotides or co-cultured with homologous T cells in the presence or absence of NTZ in vitro to determine functional effects of NTZ treatment., Results: We observed that NTZ treatment was associated with a 25-50% reduction in PDC frequency in peripheral blood as compared to untreated MS patients, while the frequency of MDCs was unchanged. PDCs in NTZ-treated patients displayed a mature, activated phenotype with increased expression of HLA-DR, TLR9, CCR7, IL-6 and IL-12. In contrast, in vitro treatment with NTZ did not increase markers of PDC activation or their ability to induce T cell differentiation., Conclusion: Our study shows that NTZ treatment is associated with a reduced frequency of PDCs in the peripheral circulation, but that PDCs in NTZ-treated individuals display an activated phenotype. Taken together the data suggests that transmigration of activated PDCs is preferentially affected by blockade of integrin α4 leading to an increased frequency of activated PDCs in blood.

Background: Osteopontin (OPN) is a pleiotropic protein with important roles in inflammation and immunity that has been suggested as a candidate biomarker for disease activity in multiple sclerosis (MS)., Objective: We evaluated plasma levels of OPN in an unselected cohort of MS patients, to determine its potential as a biomarker for disease subtype and/or disease activity in a regular clinical setting., Methods: We analyzed OPN plasma levels in 492 consecutive MS patients, using a commercial enzyme-linked immunosorbent assay (ELISA)., Results: OPN levels were higher in relapsing-remitting and secondary progressive MS, compared to healthy controls. Treatment with natalizumab or glatiramer acetate was associated with lower OPN levels. There was no significant association between the OPN levels and disease activity, as measured by clinical or radiological criteria. One-third of patients with high OPN levels had concurrent disorders that may also be associated with increased OPN expression, and which may mask a modest effect of MS disease activity on OPN levels., Conclusion: Our data do not support a role for circulating OPN levels as a biomarker for disease activity in a heterogeneous clinical setting, but does not rule out a potential role in the cerebrospinal fluid, in a controlled setting such as a clinical trial, or in concert with other biomarkers.

The article presents a study which examines plasma levels of osteopontin (OPN) in an unselected cohort of multiple sclerosis (MS) patients to determine its potential as a biomarker for disease subtype and or disease activity in a regular clinical setting. The plasma levels were analyzed in 492 consecutive MS patients through a commercial enzyme-linked immunosorbent assay (ELISA). OPN levels were found to be higher in relapsing-remitting and secondary progressive MS than healthy controls.