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Enzymatically Active ADAMTS13 Variants Are Not Inhibited by Anti-ADAMTS13 Autoantibodies: A NOVEL THERAPEUTIC STRATEGY?*
- Publication Year :
- 2005
-
Abstract
- ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motifs), a circulating multidomain zinc metalloprotease of the reprolysin subfamily, is critical for preventing von Wille-brand factor-platelet interaction under high shear stress conditions. A deficiency of the protease, due to mutations in the ADAMTS13 gene or the presence of antibodies that inhibit the activity of the protease, causes thrombotic thrombocytopenic purpura (TTP). Plasma therapy, the conventional therapy for TTP, may cause serious adverse reactions and is ineffective in some patients. In order to develop new strategies for improving the diagnosis and treatment of TTP, we produced a series of truncated ADAMTS13 proteins in mammalian cells and analyzed their binding with and suppression by the IgG derived from the TTP patients. The results revealed that truncation of the ADAMTS13 protein at its cysteine-rich region eliminated its recognition by the antibodies without abolishing its von Willebrand factor-cleaving activity. This raises the possibility that resistant ADAMTS13 variants may be exploited to circumvent inhibitory antibodies that cause TTP.
- Subjects :
- Blood Platelets
Time Factors
Purpura, Thrombotic Thrombocytopenic
Temperature
ADAMTS13 Protein
Article
Recombinant Proteins
Protein Structure, Tertiary
ADAM Proteins
hemic and lymphatic diseases
Immunoglobulin G
COS Cells
Chlorocebus aethiops
von Willebrand Factor
Animals
Humans
Immunoprecipitation
Cysteine
Autoantibodies
DNA Primers
Plasmids
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.pmid..........0a0e296bf69fa70357804df71f89c8d3