Aims: Natalizumab is a humanized monoclonal antibody specific for CD49d receptors of integrins. It inhibits the entry of inflammatory cells into the central nervous system and is approved for the treatment of relapsing-remitting multiple sclerosis (MS). Several lines of evidence indicate an involvement of B cells and plasma cells in MS pathogenesis. However, treatment with the natalizumab analogon PS/2 immunoglobulin G (IgG) has so far only been investigated in T cell-mediated animal models of MS. Due to the importance of B lineage cells in the pathogenesis of MS, the objective of the present study has thus been to analyse the effects of PS/2 IgG in a mouse model of MS with T and B cell cooperation (OSE mice).
Methods: OSE mice were treated with the natalizumab analogon PS/2 IgG either at disease onset or after peak of disease. Treatment was also performed with PS/2 F(ab')2 fragments.
Results: PS/2 IgG treatment improved the clinical outcome and decreased spinal cord demyelination and immune cell infiltration if given early in the disease course. Treatment increased blood leukocytes and resulted in a partial internalization of CD49d in T and B cells. The therapeutic effects of PS/2 IgG injections were independent of the Fc fragment as F(ab')2 injections were equally beneficial. In contrast, PS/2 IgG was not effective when given late in the disease course.
Conclusions: Results indicate that natalizumab may also be beneficial in MS with B cell-driven immunopathogenesis.
Keywords: B cells; CD49d; OSE mice; PS/2 antibody; experimental autoimmune encephalomyelitis; multiple sclerosis; natalizumab.
© 2015 British Neuropathological Society.