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

Traub, Jan W.; Pellkofer, Hannah L.; Grondey, Katja; Seeger, Ira; Rowold, Christoph; Brueck, Wolfgang; Husseini, Leila; Haeusser-Kinzel, Silke und Weber, Martin S. (2019): Natalizumab promotes activation and pro-inflammatory differentiation of peripheral B cells in multiple sclerosis patients. In: Journal of Neuroinflammation, Bd. 16, Nr. 1, 228

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch