RESUMO
BACKGROUND: Previous studies on Natalizumab (NAT) have shown increased circulation of most white blood cells (WBC) in multiple sclerosis (MS) patients shortly after its introduction. AIM: To describe peripheral immune cell phenotypes after more than 2 years of continuous NAT therapy and test for associations with clinical response to therapy. METHODS: Peripheral immune cell subsets were analyzed in 44 NAT-MS patients receiving NAT for over 24 months, and in 22 NAT-free control-MS patients. RESULTS: NAT-MS patients displayed significantly higher numbers of all WBC when compared with controls. B lymphocytes exhibited a more pronounced increase when compared with CD4+, CD8+ and NK T-cells (P = 0.011). CD4/CD8 ratio was significantly decreased in NAT-MS patients (P = 0.018) and showed no correlation with the number of NAT doses. The reduced CD4/CD8 ratio was attributable to the 'EDSS improvement' group only, irrespective of age, sex and disease severity. CONCLUSIONS: The study suggests that there is no desensitization effect after prolonged NAT exposure. A reduced CD4/CD8 ratio was associated with long-term response to therapy; thus, those patients who most benefitted from the drug might be at greater risk for opportunistic infections like progressive multifocal leucoencephalopathy (PML). We provide implications for future research for the CD4/CD8 ratio as a possible contributor to the recently developed risk stratification scheme for PML.
