Masakazu Nakamura1, Takako Matsuoka2, Norio Chihara2, Sachiko Miyake3, Wakiro Sato4, Manabu Araki5, Tomoko Okamoto4, Youwei Lin6, Masafumi Ogawa4, Miho Murata7, Toshimasa Aranami3, Takashi Yamamura8. 1. Department of Immunology, National Institute of Neuroscience, National Centre of Neurology and Psychiatry (NCNP), Tokyo, Japan Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2. Department of Immunology, National Institute of Neuroscience, National Centre of Neurology and Psychiatry (NCNP), Tokyo, Japan. 3. Department of Immunology, National Institute of Neuroscience, National Centre of Neurology and Psychiatry (NCNP), Tokyo, Japan Multiple Sclerosis Centre, National Centre Hospital, NCNP, Tokyo, Japan. 4. Multiple Sclerosis Centre, National Centre Hospital, NCNP, Tokyo, Japan Department of Neurology, National Centre Hospital, NCNP, Tokyo, Japan. 5. Multiple Sclerosis Centre, National Centre Hospital, NCNP, Tokyo, Japan. 6. Department of Immunology, National Institute of Neuroscience, National Centre of Neurology and Psychiatry (NCNP), Tokyo, Japan Multiple Sclerosis Centre, National Centre Hospital, NCNP, Tokyo, Japan Department of Neurology, National Centre Hospital, NCNP, Tokyo, Japan. 7. Department of Neurology, National Centre Hospital, NCNP, Tokyo, Japan. 8. Department of Immunology, National Institute of Neuroscience, National Centre of Neurology and Psychiatry (NCNP), Tokyo, Japan Multiple Sclerosis Centre, National Centre Hospital, NCNP, Tokyo, Japan yamamura@ncnp.go.jp.
Abstract
BACKGROUND: Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual patients indicates the need to evaluate its effects on other lymphoid cells. OBJECTIVE: To clarify the effects of fingolimod on B-cell populations in patients with MS. METHODS: We analysed blood samples from 9 fingolimod-treated and 19 control patients with MS by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts. RESULTS: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells (CD38(int-high)), particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138(+)) among whole plasmablasts, in the patients treated with fingolimod. CONCLUSIONS: The marked reduction of Ki-67(+) memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138(+) plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual patients.
BACKGROUND:Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual patients indicates the need to evaluate its effects on other lymphoid cells. OBJECTIVE: To clarify the effects of fingolimod on B-cell populations in patients with MS. METHODS: We analysed blood samples from 9 fingolimod-treated and 19 control patients with MS by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts. RESULTS: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells (CD38(int-high)), particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138(+)) among whole plasmablasts, in the patients treated with fingolimod. CONCLUSIONS: The marked reduction of Ki-67(+) memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138(+) plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual patients.
Authors: Carla Rodriguez-Mogeda; Sabela Rodríguez-Lorenzo; Jiji Attia; Jack van Horssen; Maarten E Witte; Helga E de Vries Journal: Biomolecules Date: 2022-06-07