RESUMO
BACKGROUND: Neutralizing antibodies (NAb) affect efficacy of interferon-beta (IFN-b) treatment in multiple sclerosis (MS) patients. NAbs evolve in up to 44% of treated patients, usually between 6-18 months on therapy. OBJECTIVES: To investigate whether early binding antibody (BAb) titers or different IFN-b biomarkers predict NAb evolution. METHODS: We included patients with MS or clinically isolated syndrome (CIS) receiving de novo IFN-b treatment in this prospective European multicenter study. Blood samples were collected at baseline, before and after the first IFN-b administration, and again after 3, 12 and 24 months on that therapy; for determination of NAbs, BAbs, gene expression of MxA and protein concentrations of MMP-9, TIMP-1, sTRAIL, CXCL-10 and CCL-2. RESULTS: We found that 22 of 164 (13.4%) patients developed NAbs during a median time of 23.8 months on IFN-b treatment. Of these patients, 78.9% were BAb-positive after 3 months. BAb titers ≥ 1:2400 predicted NAb evolution with a sensitivity of 74.7% and a specificity of 98.5%. Cross-sectionally, MxA levels were significantly diminished in the BAb/NAb-positive samples; similarly, CXCL-10 and sTRAIL concentrations in BAb/NAb-positive and BAb-positive/NAb-negative samples, respectively, were also diminished compared to BAb/NAb-negative samples. CONCLUSIONS: BAb titers reliably predict NAbs. CXCL-10 is a promising sensitive biomarker for IFN-b response and its abrogation by anti-IFN-b antibodies.
Assuntos
Anticorpos Neutralizantes/sangue , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/imunologia , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Interferon beta/imunologia , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/imunologia , Adulto , Biomarcadores/sangue , Quimiocina CXCL10/sangue , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/diagnóstico , Diagnóstico Precoce , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/genética , Proteínas de Resistência a Myxovirus/genética , Valor Preditivo dos Testes , Estudos Prospectivos , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
Three patients are reported on who presented with communicating hydrocephalus due to presumed tuberculous meningitis. Subsequent clinical deterioration despite antituberculous chemotherapy prompted reassessment with FDG-PET scanning and meningeal biopsy in one case and repeat CSF cytology with special staining in the second. The third patient died and postmortem confirmed a diagnosis of primary diffuse leptomeningeal gliomatosis. In the first two patients, MRI of the entire neuraxis showed no evidence of a primary intraparenchymal tumour. These cases emphasise the need for repeated reassessment in patients with culture negative lymphocytic meningitis. In addition, this is the first report of FDG-PET scanning in leptomeningeal gliomatosis.
