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PLoS One ; 15(7): e0235449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716916

RESUMO

BACKGROUND: Several disease modifying drugs (DMDs) have been approved for the treatment of multiple sclerosis (MS), however, little is known about their differential impact on peripheral blood (PB) B cell subsets. METHODS: We performed a cross sectional study on PB B cells in MS patients treated with interferon-ß (n = 25), glatiramer acetate (n = 19), dimethyl fumarate (n = 15), fingolimod (n = 16) or natalizumab (n = 22), untreated MS patients (n = 20), and in patients with non-inflammatory neurological diseases (n = 12). Besides analyzing routine laboratory data, flow cytometry was performed to analyze naïve B cells (CD19+CD20+CD27-IgD+), non-class switched (CD19+CD20+CD27+IgD+) and class-switched memory B cells (CD19+CD20+CD27+IgD-), double negative B cells (CD19+CD20lowCD27-IgD-) and plasmablasts (CD19+CD20lowCD27+CD38++). RESULTS: Treatment associated changes were found for the overall B cell pool as well as for all B cell subsets. Natalizumab increased absolute numbers and percentage of all B cells mainly by expanding the memory B cell pool. Fingolimod decreased absolute numbers of all B cell subsets and the percentage of total B cells. Fingolimod, dimethyl fumarate and interferon-ß treatments were associated with an increase in the fraction of naïve B cells while class switched and non-class switched memory B cells showed decreased percentages. CONCLUSION: Our results highlight differential effects of DMDs on the PB B cell compartment. Across the examined treatments, a decreased percentage of memory B cells was found in dimethyl fumarate, interferon-ß and fingolimod treated patients which might contribute to the drugs' mode of action in MS. Further studies are necessary to decipher the exact role of B cell subsets during MS pathogenesis.


Assuntos
Subpopulações de Linfócitos B/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Memória Imunológica/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/classificação , Antígenos CD/imunologia , Antígenos CD19 , Subpopulações de Linfócitos B/classificação , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Estudos Transversais , Fumarato de Dimetilo/administração & dosagem , Feminino , Cloridrato de Fingolimode/administração & dosagem , Citometria de Fluxo , Acetato de Glatiramer/administração & dosagem , Humanos , Memória Imunológica/imunologia , Imunofenotipagem , Imunossupressores/administração & dosagem , Imunossupressores/imunologia , Interferon beta/administração & dosagem , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Natalizumab/administração & dosagem , Adulto Jovem
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