Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 42, Issue 3, Pages 790-798Publisher
WILEY
DOI: 10.1002/eji.201142108
Keywords
B cells; Multiple sclerosis; Natalizumab; Progressive multifocal leukoencephalopathy
Categories
Funding
- Gemeinnutzige Hertie Stiftung
- Deutsche Forschungsgemeinschaft [JE 530/1-1]
Ask authors/readers for more resources
Natalizumab, an antibody against the a4 subunit of a4 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), na?ve, effector or memory T cells remained unchanged during treatment, a higher percentage of memory- and marginal zone (MZ)-like, but not of na?ve 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available