| Autor: |
Hoffmann, S., Cepok, S., Grummel, V., Lehmann-Horn, K., Hackermüller, J., Stadler, P.F., Hartung, H.-P., Berthele, A., Deisenhammer, F., Wasmuth, R., Hemmer, B. |
| Přispěvatelé: |
Publica |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Předmět: |
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| Popis: |
The formation of antibodies to interferon-beta (IFN-beta), a protein-based disease-modifying agent for multiple sclerosis (MS), is a problem in clinical practice. These antibodies may neutralize the biological effects of the protein drug, potentially decreasing its therapeutic effects. By high-resolution HLA class I and II typing we identified two HLA class II alleles associated with the development of antibodies to IFN-beta. In two independent continuous and binary-trait association studies, HLA-DRB1*0401 and HLA-DRB1*0408 (odds ratio: 5.15)-but not other HLA alleles-were strongly associated with the development of binding and neutralizing antibodies to IFN-beta. The associated HLA-DRB1*04 alleles differ from nonassociated HLA-DRB1*04 alleles by a glycine-to-valine substitution in position 86 of the epitope-binding alpha-helix of the HLA class II molecule. The peptide-binding motif of HLA-DRB1*0401 and *0408 might promote binding and presentation of an immunogenic peptide, which may eventually break T cell tolerance and facilitate antibody development to IFN-beta. In summary, we identified genetic factors determining the immunogenicity of IFN-beta, a protein-based disease-modifying agent for the treatment of MS. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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