Pharmacodynamics of interferon beta in multiple sclerosis patients with or without serum neutralizing antibodies
| Autor: | Francesca Bagnato, Maria Trojano, Ludwig Kappos, Petra Duda, Alessia Alberelli, Valentina Durastanti, Guido Antonelli, Gabriella De Vito, Vito Lavolpe, Enrico Girardi, Carolina Scagnolari |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Myxovirus Resistance Proteins medicine.medical_specialty Multiple Sclerosis Gene Expression Neopterin Antibodies Statistics Nonparametric Antigen-Antibody Reactions Disability Evaluation eIF-2 Kinase chemistry.chemical_compound GTP-Binding Proteins Neutralization Tests In vivo Internal medicine beta2-microglobulin interferon beta multiple sclerosis mxa neopterin neutralizing antibodies pkr medicine Humans RNA Messenger Beta (finance) biology Reverse Transcriptase Polymerase Chain Reaction Beta-2 microglobulin business.industry Multiple sclerosis Interferon-beta Middle Aged medicine.disease Titer Endocrinology Neurology chemistry Pharmacodynamics Immunology biology.protein Female Neurology (clinical) Antibody beta 2-Microglobulin business |
| Zdroj: | Journal of Neurology. 254:597-604 |
| ISSN: | 1432-1459 0340-5354 |
| DOI: | 10.1007/s00415-006-0332-7 |
| Popis: | To analyze the in vivo biological effect of anti-interferon beta (IFN-beta) neutralizing antibodies (NABs), blood concentrations of neopterin, beta2microglobulin (Beta2-MG), mRNA-dependent myxovirusresistant protein A (MxA) and dsRNA-dependent protein kinase (PKR) were measured before (predose) and 24 hours after (postdose) IFN-beta administration in 49 patients with multiple sclerosis (MS) with (n = 25) and without (n = 24) NABs. The results indicated that predose levels of MxA-mRNA and PKR-mRNA were highly variable [coefficient of variation (CV) > 100%] among patients. A lower inter-individual variability was observed for pre-dose levels of Beta2-MG and neopterin (CVs of 29% and 44%, respectively). Significantly lower pre- and post-dose blood levels of IFN induced markers, except for postdose PKR-mRNA (p = 0.09), were seen in NAB+ compared with NAB-patients and between patients with high (> 200 t1/10) and low (£ 200 t1/10) NAB titers. A significant inverse correlation between NAB titer and pre-dose levels of the above IFN-induced markers was found. In summary, our findings confirm that NABs affect absolute concentrations of IFN-beta induced markers and suggest that such an effect occurs in a titer-dependent manner |
| Databáze: | OpenAIRE |
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