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1.
J Neuroimmunol ; 337: 577085, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31655423

RESUMO

The objectives were to study the expression of very late antigen (VLA)-4, melanoma cell adhesion molecule-1 (MCAM-1) and activated leukocyte cell adhesion molecule (ALCAM) on CD4+ T cells during natalizumab treatment and to investigate the association with disease activity. We find that subgroups of autoreactive T cells are retained in peripheral blood, in particular MOG-reactive CD4+ T cells expressing MCAM-1. The expression of MCAM-1 or ALCAM on CD4+ T cells was, however, not clearly associated with disease activity (clinical or MRI) during natalizumab treatment. We confirm upregulation of MCAM-1 on CD4+ T cells during natalizumab treatment while VLA-4 is downregulated.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Fatores Imunológicos/administração & dosagem , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Natalizumab/administração & dosagem , Adulto , Idoso , Antígeno CD146/biossíntese , Antígeno CD146/sangue , Linfócitos T CD4-Positivos/efeitos dos fármacos , Estudos de Coortes , Feminino , Expressão Gênica , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
2.
Pharmacogenomics J ; 16(2): 141-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25939484

RESUMO

At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.


Assuntos
Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , MicroRNAs/sangue , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Artrite Reumatoide/genética , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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