Differential effects of fingolimod on B-cell populations in multiple sclerosis.
Mult Scler
; 20(10): 1371-80, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24526661
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Propilenoglicóis
/
Esfingosina
/
Subpopulações de Linfócitos B
/
Imunossupressores
/
Esclerose Múltipla
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article