Background: Treatment with natalizumab, a humanized monoclonal antibody against alpha4beta1 integrin, is associated with an increase in lymphoid progenitor cells and B cells in peripheral blood.
Objective: The objective of this study was to examine the impact of natalizumab therapy on serum levels of total IgG, IgA and IgM in patients with multiple sclerosis (MS).
Methods: In two independent cross-sectional patient cohorts, serum levels of IgG, IgA and IgM were compared between patients treated with natalizumab and those not receiving natalizumab. Further, serum levels of IgG, IgA and IgM before and during natalizumab treatment were compared in two longitudinal patient cohorts.
Results: In patients treated with natalizumab, serum IgM and IgG levels were significantly lower compared with therapy naïve patients (p<0.0001). IgM levels significantly decreased after initiation of natalizumab treatment in both longitudinal patient cohorts (p<0.01). Moreover, patients treated with natalizumab showed a time-dependent decrease in IgM levels during the first 2 years of treatment.
Conclusion: Natalizumab treatment leads to a significant decrease in serum IgM and IgG levels in patients with MS. IgM levels decrease with treatment duration during the first 2 years of treatment. These findings might support the hypothesis that natalizumab interferes with homing of B cells, possibly leading to impaired differentiation into plasma cells and subsequently disturbed immunoglobulin synthesis.
Keywords: B cell homing; Multiple sclerosis; alpha4beta1 integrin; immunoglobulin G; immunoglobulin M; natalizumab.