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Natalizumab treatment perturbs memory‐ and marginal zone‐like B‐cell homing in secondary lymphoid organs in multiple sclerosis

2011; Wiley; Volume: 42; Issue: 3 Linguagem: Inglês

10.1002/eji.201142108

1521-4141

Raquel Planas, Ilijas Jelčić, Sven Schippling, Roland Martinꝉ, Mireia Sospedra,

RNA Interference and Gene Delivery

Natalizumab, an antibody against the α4 subunit of α4 integrins, has been approved for multiple sclerosis (MS) therapy based on its high efficacy and safety profile. However, natalizumab has been associated with the development of progressive multifocal leukoencephalopathy (PML), a disorder caused by JC virus (JCV) infection. In order to improve our understanding of the mechanism of action of natalizumab and to identify possible risk factors for PML development, we have characterized in detail the cell blood composition in MS patients treated with natalizumab for more than 30 months. Natalizumab induced the release of lymphoid- but not myeloid precursor cells, which resulted in a chronic increase ofT-, NK- and particularly B cells. While the percentage of recent thymic emigrants (RTEs), naϊve, effector or memory T cells remained unchanged during treatment, a higher percentage of memory- and marginal zone (MZ)-like, but not of naϊve B cells, was observed, which most likely is due to a decreased retention of these cells within the splenic MZ. The ability of natalizumab to influence B-cell migration and homeostasis through the splenic MZ, where JCV has been detected, adds to the list of natalizumab effects and may contribute to PML development by disseminating JCV.