| Autor: |
Tiarks, C., Humphreys, R. E., Anderson, J., Mole, J., Pechet, L. |
| Předmět: |
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| Zdroj: |
Scandinavian Journal of Immunology; Nov1992, Vol. 36 Issue 5, p653-660, 8p |
| Abstrakt: |
The study of the immunobiology of FVIII inhibitors may lead to new therapies for this potentially severe complication of haemophilia A and to new principles for the use of therapeutic proteins. In order to characterize the idiotype-anti-idiotype networks regulating FVIII inhibitors, we developed rabbit anti-idiotypic sera to 7 murine inhibitors and found at least 12 independent FVIII loci to which inhibitors could be raised. Rabbit antisera lo the FVIII peptide, Ser1687-Thr1695 characterized one functional site to which about 46% of patients' inhibitor sera reacted. The multiplicity of inhibitor-recognized epitopes in FVIII makes it impractical, at the present time, to develop clinically useful specific anti-idiotypic therapies for FVIII inhibitors. Alternatively, one might induce genomic mutations in recombinant FVIII molecules to decrease immunogenicity of epitopes recognized by T helper cells. Methods to design such altered therapeutic proteins are presented, based on changing the longitudinal hydrophobic strip of- helix which is in or near many T-cell-presented epitopes. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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