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Natalizumab promotes activation and pro-inflammatory differentiation of peripheral B cells in multiple sclerosis patients.

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Published:16th Nov 2019
Author: Traub JW, Pellkofer HL, Grondey K, Seeger I, Rowold C, Brück W et al.
Availability: Free full text
Ref.:J Neuroinflammation. 2019;16(1):228.
DOI:10.1186/s12974-019-1593-2


Background:
In the past, multiple sclerosis (MS) medications have been primarily designed to modulate T cell properties. Based on the emerging concept that B cells are equally important for the propagation of MS, we compared the effect of four commonly used, primarily T cell-targeting MS medications on B cells.

Methods: Using flow cytometry, we analyzed peripheral blood mononuclear cells (PBMC) of untreated (n = 19) and dimethyl fumarate (DMF; n = 21)-, fingolimod (FTY; n = 17)-, glatiramer acetate (GA; n = 18)-, and natalizumab (NAT; n = 20)-treated MS patients, focusing on B cell maturation, differentiation, and cytokine production.

Results: While GA exerted minor effects on the investigated B cell properties, DMF and FTY robustly inhibited pro-inflammatory B cell function. In contrast, NAT treatment enhanced B cell differentiation, activation, and pro-inflammatory cytokine production when compared to both intraindividual samples collected before NAT treatment initiation as well as untreated MS controls. Our mechanistic in vitro studies confirm this observation.

Conclusion: Our data indicate that common MS medications have differential, in part opposing effects on B cells. The observed activation of peripheral B cells upon NAT treatment may be instructive to interpret its unfavorable effect in certain B cell-mediated inflammatory conditions and to elucidate the immunological basis of MS relapses after NAT withdrawal.

Trial registration: Protocols were approved by the ethical review committee of the University Medical Center Göttingen (#3/4/14).

 

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