Differential effects of fingolimod on B-cell populations in multiple sclerosis

芬戈莫德对多发性硬化症 B 细胞群的不同影响

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作者:Masakazu Nakamura, Takako Matsuoka, Norio Chihara, Sachiko Miyake, Wakiro Sato, Manabu Araki, Tomoko Okamoto, Youwei Lin, Masafumi Ogawa, Miho Murata, Toshimasa Aranami, Takashi Yamamura

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.

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.

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.

Objective

To clarify the effects of fingolimod on B-cell populations in patients with MS.

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.

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