RESUMO
Progressive multifocal leukoencephalopathy (PML) is the main adverse effect of natalizumab. Detectable JC virus-specific effector memory T-cell (TEM) responses may indicate ongoing JCV replication. We detected JCV-specific TEM responses in blood of patients with multiple sclerosis (MS) treated with natalizumab, including 2 patients with PML. The frequency of detection of these responses increased with the time on natalizumab. Thus, a subset of MS patients exhibit immunological hallmarks of JCV replication during prolonged natalizumab therapy.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Produtos Biológicos/efeitos adversos , Fatores Imunológicos/efeitos adversos , Vírus JC/imunologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Replicação Viral , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Produtos Biológicos/administração & dosagem , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Vírus JC/fisiologia , Pessoa de Meia-Idade , Esclerose Múltipla/virologia , Natalizumab , Linfócitos T/imunologiaRESUMO
Blood angiotensin-converting enzyme (ACE) assay is now realized by the determination of enzyme activity on synthetic substrate, mostly furylacryloyl-phenylalanyl-L-glycyl-L-glycine (FAPGG). The matrix can be serum or heparin-plasma, with or without a separator; the assay developed on serum or plasma is not adapted to other matrix such as cerebrospinal fluid where the ACE activity is much lower. This assay has been adapted on a number of automated biochemistry analyzers with the specifications of the supplier of reagents, sometimes with modification of volumes or times for analysis. Samples can be stored at +4ÌC for at least for one week, freezing at -20ÌC is possible but refreezing is not advised. The assay is linear from 10 to 200 UI/L. Fidelity is excellent after calibration of the assay. Accuracy can be calculated from IQA and EQA results, and the analytical uncertainty is between 2% and 5% in function of the serum ACE value. Usual values will be soon available from studies on age brackets and sex, because ACE activity seems to be more elevated in boys during adolescence. At signature, it is interesting to have medical information on the diagnosis of sarcoidosis or its treatment including ACE inhibitors as a proof of intake; we can give a commentary on elevation of serum ACE activity from other causes than sarcoidosis and the causes for low activities.