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Natalizumab treatment promotes activation and differentiation of peripheral B cells in multiple sclerosis
Author(s): ,
L. Husseini
Affiliations:
University Medical Centre, Department of Neurology
,
I. Seeger
Affiliations:
University Medical Centre, Institute of Neuropathology, Göttingen, Germany
,
C. Rowold
Affiliations:
University Medical Centre, Department of Neurology
,
W. Brück
Affiliations:
University Medical Centre, Institute of Neuropathology, Göttingen, Germany
M. Weber
Affiliations:
University Medical Centre, Department of Neurology; University Medical Centre, Institute of Neuropathology, Göttingen, Germany
ECTRIMS Online Library. Husseini L.
Oct 12, 2018; 229057
Leila Husseini
Leila Husseini
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Abstract: P1217

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

Background: Natalizumab, a monoclonal antibody to alpha-4-integrin, is a highly effective treatment of relapsing-remitting multiple sclerosis (MS). The binding of natalizumab to very late antigen-4 (VLA-4) expressed on the surface of lymphocytes blocks their entry into the central nervous system. Furthermore, natalizumab leads to changes of circulating immune cells in the periphery, especially with an increased frequency of lymphocytes belonging to the B cell lineage.
Methods: We characterized B cell properties in peripheral blood mononuclear cells obtained from natalizumab-treated MS patients (n = 18) and compared them to untreated MS patients (n = 19). In four additional MS patients, we analysed B cell properties longitudinally before and after the start of natalizumab treatment.
Results: In natalizumab-treated patients, the overall frequency of CD19 positive B cells was increased, with a significant expansion of memory and transitional B cells. Furthermore, the expression of activation markers CD69, CD80 and CD86 was significantly higher on B cells from natalizumab-treated patients compared to untreated controls. After natalizumab treatment initiation, a significant increase in the production of pro-inflammatory tumor necrosis factor (TNF) by B cells could be measured upon ex vivo stimulation. Current experiments aim to elucidate by which mechanism natalizumab mediates the observed alterations in the B cell compartment.
Conclusion: In patients with MS, treatment with natalizumab activates B cells and promotes their differentiation and pro-inflammatory function. The increased frequency and activation state of circulating B cells may explain why natalizumab exacerbates disease in patients with neuromyelitis optica. Furthermore, these findings may help to understand the disease exacerbation seen in individual patients after natalizumab withdrawal.
Disclosure: L. Husseini receives research support from Novartis. L. Husseini received speaker honoraria from Bayer. I. Seeger: nothing to disclose. Ch. Rowold receives the VorSPrUNG scholarship of the Universitätsmedizin Göttingen. M. Weber receives research support from the Deutsche Forschungsgemeinschaft (DFG; WE 3547/5-1), from Novartis, TEVA, Biogen-Idec, Roche, Merck and the ProFutura Programm of the Universitätsmedizin Göttingen. M. Weber is serving as an editor for PLoS One. He received travel funding and/or speaker honoraria from Biogen-Idec, Merck Serono, Novartis, Roche, TEVA, Bayer and Genzyme.

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