Contributions
Abstract: P1210
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Alemtuzumab is a humanised monoclonal antibody that recognises CD52, a protein expressed on the surface of mature lymphocytes. It has been approved for the treatment of relapsing remitting multiple sclerosis (RRMS). Altrhough it has been postulated that it induce reprogramming of the abnormal immune response in MS, the particular changes in leucocyte subsets have not been fully ascertained.
Objective: To deepen the study of changes in blood immune cells induces by alemtuzumab in an exploratory cohort of MS patients.
Methods: We studied peripheral blood mononuclear cells of 8 patients diagnosed with RRMS and treated with this drug before treatment and after 12 months before the second cycle of alemtuzumab. We explored different CD4, CD8 T cell subsets, B cell subpopulations and monocytes and intracellular cytokine production.
Results: We observed a decrease in the total number of CD4+ T cells (p=0.03), regulatory T cells (p=0.03) and central memory CD4+ (p=0.01) and CD8+ (p=0.03) T cells. Numbers of plasmablasts were also decreased (p=0.01) and memory B cells (p=0.01) increased. Additionally, we observed an increase in number of regulatory NK cells (p=0.007) and a decrease in NKT cells (p=0.007). The production of GM-CSF by T cells (p=0.007 in CD8+ and p=0.01 in CD4+) and production of TNF-alfa by CD4+ T cells (p=0.007) and B cells (p=0.01) were also decreased. In addition, we quantified the production of different cytokines by measuring the mean fluorescence intensity (MFI) and observed a decrease in the production of GM-CSF by CD8+ T cells (p=0.007), and TNF-alfa by CD4+ T cells (p=0.01) and B cells (0.007).
Conclusions: Alemtuzumab treatment induces an increase in regulatory NK cells and a decrease in effector cells with the exception of memory B cells that increased with this treatment. We also observed a decrease in proinflamatory cytokine production.
Disclosure: S. Medina: Nothing to disclose. S. Sainz de la Maza: received payment for lecturing from Novartis, Biogen, Roche and Merck. N. Villarrubia: Nothing to disclose. J.C. Álvarez-Cermeño: received payment for lecturing or research grants from Merck, Novartis, Biogen, Roche, Bayer, Teva, and Sanofi-Genzyme. E. Monreal: Nothing to disclose. A. Tejeda-Velarde: Nothing to disclose. E. Rodríguez-Martín: Nothing to disclose. L. Costa-Frossard: received payment for lecturing from Novartis, Biogen, Roche, Bayer and Sanofi- Genzyme. L.M. Villar: received payment for lecturing or research grants from Merck, Novartis, Biogen, Roche and Sanofi- Genzyme.
Funding: FIS-PI15/00513 and RD16/0015/0001.
Abstract: P1210
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Alemtuzumab is a humanised monoclonal antibody that recognises CD52, a protein expressed on the surface of mature lymphocytes. It has been approved for the treatment of relapsing remitting multiple sclerosis (RRMS). Altrhough it has been postulated that it induce reprogramming of the abnormal immune response in MS, the particular changes in leucocyte subsets have not been fully ascertained.
Objective: To deepen the study of changes in blood immune cells induces by alemtuzumab in an exploratory cohort of MS patients.
Methods: We studied peripheral blood mononuclear cells of 8 patients diagnosed with RRMS and treated with this drug before treatment and after 12 months before the second cycle of alemtuzumab. We explored different CD4, CD8 T cell subsets, B cell subpopulations and monocytes and intracellular cytokine production.
Results: We observed a decrease in the total number of CD4+ T cells (p=0.03), regulatory T cells (p=0.03) and central memory CD4+ (p=0.01) and CD8+ (p=0.03) T cells. Numbers of plasmablasts were also decreased (p=0.01) and memory B cells (p=0.01) increased. Additionally, we observed an increase in number of regulatory NK cells (p=0.007) and a decrease in NKT cells (p=0.007). The production of GM-CSF by T cells (p=0.007 in CD8+ and p=0.01 in CD4+) and production of TNF-alfa by CD4+ T cells (p=0.007) and B cells (p=0.01) were also decreased. In addition, we quantified the production of different cytokines by measuring the mean fluorescence intensity (MFI) and observed a decrease in the production of GM-CSF by CD8+ T cells (p=0.007), and TNF-alfa by CD4+ T cells (p=0.01) and B cells (0.007).
Conclusions: Alemtuzumab treatment induces an increase in regulatory NK cells and a decrease in effector cells with the exception of memory B cells that increased with this treatment. We also observed a decrease in proinflamatory cytokine production.
Disclosure: S. Medina: Nothing to disclose. S. Sainz de la Maza: received payment for lecturing from Novartis, Biogen, Roche and Merck. N. Villarrubia: Nothing to disclose. J.C. Álvarez-Cermeño: received payment for lecturing or research grants from Merck, Novartis, Biogen, Roche, Bayer, Teva, and Sanofi-Genzyme. E. Monreal: Nothing to disclose. A. Tejeda-Velarde: Nothing to disclose. E. Rodríguez-Martín: Nothing to disclose. L. Costa-Frossard: received payment for lecturing from Novartis, Biogen, Roche, Bayer and Sanofi- Genzyme. L.M. Villar: received payment for lecturing or research grants from Merck, Novartis, Biogen, Roche and Sanofi- Genzyme.
Funding: FIS-PI15/00513 and RD16/0015/0001.