Contributions
Abstract: EP1590
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Objective: To analyze whether commonly used multiple sclerosis (MS) disease-modifying drugs may induce changes in B cell subset distribution and/or cytokine production capacities of B cells.
Methods: We prospectively enrolled RRMS patients naive of any disease modifying drugs. Blood samples were collected at baseline, and 3, 6 and 12 months after initiation of treatment. To determine both peripheral blood B cell subset distribution and functions, a phenotypic analysis by cytometry was performed. The proportions of IL-6- and of IL-10-producing B cells were measured, after polyclonal stimulation, to assess pro-inflammatory and anti-inflammatory functional properties of peripheral blood B cells. Changes in either lymphocyte subset numbers or percentages (as appropriate) were analysed by building a mixed model of repeated measurements for each lymphocyte subset (SAS® 9.4 software).
Results: Of the 46 RRMS patients included: 18 were treated by beta-interferon (IFN-β), 17 by dimethylfumarate (DMF) and 11 by teriflunomide (TFM). Although no significant decrease in total B cell counts could be considered in either of the 3 treatment groups, significant changes were evidenced in B cell subset distribution. IFN-β initiation was associated with an increase of transitional B cell (p< 0.001) and a decrease of marginal zone B cell (p< 0.003) proportions from the 3rd month of treatment. IFN-β also induced an increase of the IL-10-producing B cell proportion from the 6th month (p< 0.001), without any change of the IL-6-producing B cells. DMF initiation was associated with a decrease of all memory B cell subset (p< 0.001) proportions from the 6th month, and with an increase of the mature naive B cell proportion at 12 months (p=0.005). No variation in IL-10 or IL-6-producing B cell proportions was observed. Under TFM initiation, no significant modification of the B cell subset distribution was observed, while both the IL10- and IL-6-producing B cell proportions decreased (p=0.02 and p=0.04 respectively) at 12 months.
Conclusions: TFM is associated with a decrease in pro- as well as anti-inflammatory B cell properties. Conversely, IFN-β and DMF induced significant changes in B cell subset distribution, which were, for IFN-β, notably associated with changes in functional properties leading to an increase of potentially regulatory IL-10-producing B cells. These effects on B cells appear early with IFN-β and delayed with DMF.
Disclosure: Thomas Guerrier received research fellowships from Fondation pour la Recherche, Université Lille 2 and ARSEP as well as research grants from Université Lille 2 and ARSEP and research supports from GENZYME.
Benjamin Lopez has nothing to disclose.
Myriam Labalette received grant from Maco Pharma.
Olivier Outteryck received consulting fees, and invitations for national and international congresses from BIOGEN, MERCK, TEVA, SANOFI-GENZYME, NOVARTIS, BAYER, and ROCHE as well as research supports from BIOGEN, BAYER and NOVARTIS, and academic research grants from VISIO Foundation.
David Launay received grants and consulting fees from GSK, PFIZER, ACTELION, OCTAPHARMA and SHIRE.
Guillaume Lefèvre received consulting fees, and invitations for national and international congresses, from LFB, OCTAPHARMA, and SHIRE, as well as research supports from LFB, CSL BEHRING, AIR LIQUIDE, OCTAPHARMA, GRIFFOLS and GSK
Patrick Vermersch received honoraria and consulting fees from BIOGEN IDEC, SANOFI-GENZYME, BAYER, NOVARTIS, TEVA, MERCK, ROCHE and ALMIRALL, as well as research supports from BIOGEN, BAYER, NOVARTIS, SANOFI-GENZYME, ROCHE and MERCK.
Sylvain Dubucquoi received consulting fees, and invitations for national and international congresses, from BIOGEN and TEVA, as well as research supports from GENZYME, OCTAPHARMA, ROCHE, CSL BEHRING and NOVARTIS, and academic research grants from Lille University and ARSEP Foundation.
Hélène Zéphir received fees for consulting or lectures, and invitations for national and international congresses from BIOGEN, MERCK, TEVA, SANOFI-GENZYME, NOVARTIS and BAYER, as well as research support from TEVA and ROCHE, and academic research grants from Académie de Médecine, LFSEP, and ARSEP Foundation.
Abstract: EP1590
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Objective: To analyze whether commonly used multiple sclerosis (MS) disease-modifying drugs may induce changes in B cell subset distribution and/or cytokine production capacities of B cells.
Methods: We prospectively enrolled RRMS patients naive of any disease modifying drugs. Blood samples were collected at baseline, and 3, 6 and 12 months after initiation of treatment. To determine both peripheral blood B cell subset distribution and functions, a phenotypic analysis by cytometry was performed. The proportions of IL-6- and of IL-10-producing B cells were measured, after polyclonal stimulation, to assess pro-inflammatory and anti-inflammatory functional properties of peripheral blood B cells. Changes in either lymphocyte subset numbers or percentages (as appropriate) were analysed by building a mixed model of repeated measurements for each lymphocyte subset (SAS® 9.4 software).
Results: Of the 46 RRMS patients included: 18 were treated by beta-interferon (IFN-β), 17 by dimethylfumarate (DMF) and 11 by teriflunomide (TFM). Although no significant decrease in total B cell counts could be considered in either of the 3 treatment groups, significant changes were evidenced in B cell subset distribution. IFN-β initiation was associated with an increase of transitional B cell (p< 0.001) and a decrease of marginal zone B cell (p< 0.003) proportions from the 3rd month of treatment. IFN-β also induced an increase of the IL-10-producing B cell proportion from the 6th month (p< 0.001), without any change of the IL-6-producing B cells. DMF initiation was associated with a decrease of all memory B cell subset (p< 0.001) proportions from the 6th month, and with an increase of the mature naive B cell proportion at 12 months (p=0.005). No variation in IL-10 or IL-6-producing B cell proportions was observed. Under TFM initiation, no significant modification of the B cell subset distribution was observed, while both the IL10- and IL-6-producing B cell proportions decreased (p=0.02 and p=0.04 respectively) at 12 months.
Conclusions: TFM is associated with a decrease in pro- as well as anti-inflammatory B cell properties. Conversely, IFN-β and DMF induced significant changes in B cell subset distribution, which were, for IFN-β, notably associated with changes in functional properties leading to an increase of potentially regulatory IL-10-producing B cells. These effects on B cells appear early with IFN-β and delayed with DMF.
Disclosure: Thomas Guerrier received research fellowships from Fondation pour la Recherche, Université Lille 2 and ARSEP as well as research grants from Université Lille 2 and ARSEP and research supports from GENZYME.
Benjamin Lopez has nothing to disclose.
Myriam Labalette received grant from Maco Pharma.
Olivier Outteryck received consulting fees, and invitations for national and international congresses from BIOGEN, MERCK, TEVA, SANOFI-GENZYME, NOVARTIS, BAYER, and ROCHE as well as research supports from BIOGEN, BAYER and NOVARTIS, and academic research grants from VISIO Foundation.
David Launay received grants and consulting fees from GSK, PFIZER, ACTELION, OCTAPHARMA and SHIRE.
Guillaume Lefèvre received consulting fees, and invitations for national and international congresses, from LFB, OCTAPHARMA, and SHIRE, as well as research supports from LFB, CSL BEHRING, AIR LIQUIDE, OCTAPHARMA, GRIFFOLS and GSK
Patrick Vermersch received honoraria and consulting fees from BIOGEN IDEC, SANOFI-GENZYME, BAYER, NOVARTIS, TEVA, MERCK, ROCHE and ALMIRALL, as well as research supports from BIOGEN, BAYER, NOVARTIS, SANOFI-GENZYME, ROCHE and MERCK.
Sylvain Dubucquoi received consulting fees, and invitations for national and international congresses, from BIOGEN and TEVA, as well as research supports from GENZYME, OCTAPHARMA, ROCHE, CSL BEHRING and NOVARTIS, and academic research grants from Lille University and ARSEP Foundation.
Hélène Zéphir received fees for consulting or lectures, and invitations for national and international congresses from BIOGEN, MERCK, TEVA, SANOFI-GENZYME, NOVARTIS and BAYER, as well as research support from TEVA and ROCHE, and academic research grants from Académie de Médecine, LFSEP, and ARSEP Foundation.