Contributions
Abstract: P1214
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: B cells may contribute to the immunopathogenesis of multiple sclerosis (MS) through antigen presentation, cytokine secretion, and antibody production. Dimethyl fumarate (DMF), used for treating relapsing-remitting MS, has recently been shown to reduce the frequency of memory B cells in blood, but it is not known whether the drug affects B cells in the central nervous system.
Methods: We analyzed mononuclear cells from blood and cerebrospinal fluid (CSF) from untreated (n=7) and DMF-treated (n=10) MS patients. B cells were identified by the surface expression of CD19 and classified as CD27+CD38- memory B cells or CD27+CD38+ plasmablasts. Additionally, we assayed the subpopulations for the expression of human leukocyte antigen (HLA)-DR, immunoglobulin G, CD138, and the proliferation marker Ki-67.
Results: We demonstrate that patients treated with DMF have a reduced proportion of memory B cells in blood compared to untreated patients (p=0.012), and that the reduction correlates with treatment duration (rs = -0.75, p=0.021). In the CSF, we did not observe a similar reduction in memory B cells, but rather a disproportionate reduction of plasmablasts (p=0.039). Further phenotyping of the subpopulations revealed that DMF treatment is associated with a reduced expression of HLA-DR among memory B cells, indicating an impaired ability to present antigens to T cells, but this was only significant in blood.
Conclusion: These results support a B-cell mediated mechanism of action for DMF, and demonstrate how this manifests in blood and CSF.
Disclosure: RAH has received speaker honoraria and/or received unrestricted research grants from Biogen, Merck, Novartis and Roche. TH has received speaker honoraria, and/or served on advisory board, and/or received unrestricted research grants from Biogen, Roche, Merck, Novartis, and Genzyme. AL has received speaker honoraria from Roche, and unrestricted research grants from Sanofi Genzyme. JP: nothing to disclose. FV: nothing to disclose. The study was supported by the South-Eastern Norway Regional Health Authority (grant 2016079) and the Norwegian Research Council (grant 250864/F20).
Abstract: P1214
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: B cells may contribute to the immunopathogenesis of multiple sclerosis (MS) through antigen presentation, cytokine secretion, and antibody production. Dimethyl fumarate (DMF), used for treating relapsing-remitting MS, has recently been shown to reduce the frequency of memory B cells in blood, but it is not known whether the drug affects B cells in the central nervous system.
Methods: We analyzed mononuclear cells from blood and cerebrospinal fluid (CSF) from untreated (n=7) and DMF-treated (n=10) MS patients. B cells were identified by the surface expression of CD19 and classified as CD27+CD38- memory B cells or CD27+CD38+ plasmablasts. Additionally, we assayed the subpopulations for the expression of human leukocyte antigen (HLA)-DR, immunoglobulin G, CD138, and the proliferation marker Ki-67.
Results: We demonstrate that patients treated with DMF have a reduced proportion of memory B cells in blood compared to untreated patients (p=0.012), and that the reduction correlates with treatment duration (rs = -0.75, p=0.021). In the CSF, we did not observe a similar reduction in memory B cells, but rather a disproportionate reduction of plasmablasts (p=0.039). Further phenotyping of the subpopulations revealed that DMF treatment is associated with a reduced expression of HLA-DR among memory B cells, indicating an impaired ability to present antigens to T cells, but this was only significant in blood.
Conclusion: These results support a B-cell mediated mechanism of action for DMF, and demonstrate how this manifests in blood and CSF.
Disclosure: RAH has received speaker honoraria and/or received unrestricted research grants from Biogen, Merck, Novartis and Roche. TH has received speaker honoraria, and/or served on advisory board, and/or received unrestricted research grants from Biogen, Roche, Merck, Novartis, and Genzyme. AL has received speaker honoraria from Roche, and unrestricted research grants from Sanofi Genzyme. JP: nothing to disclose. FV: nothing to disclose. The study was supported by the South-Eastern Norway Regional Health Authority (grant 2016079) and the Norwegian Research Council (grant 250864/F20).