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| http://dx.doi.org/10.3324/haematol.2019.219063 | DOI Listing |
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Unraveling antibody-induced structural dynamics in the ADAMTS13 CUB1-2 domains via HDX-MS.
Blood Adv
January 2025
KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
Allosteric regulation of ADAMTS13 (A Disintegrin And Metalloproteinase with ThromboSpondin type-1 motif, member 13) activity involves an interaction between its Spacer (S) and CUB1-2 domains to keep the enzyme in a closed, latent conformation. Monoclonal antibodies (mAb) uncouple the S-CUB interaction to open the ADAMTS13 conformation and thereby disrupt the global enzyme latency. The molecular mechanism behind this mAb-induced allostery remains poorly understood.
View Article and Find Full Text PDFComplex immunogenicity assessment in caplacizumab-treated patients with immune-mediated thrombotic thrombocytopenic purpura who have received plasma exchange.
Res Pract Thromb Haemost
November 2024
Sanofi, Ghent, Belgium.
Background: International Society on Thrombosis and Haemostasis guidelines for immune-mediated thrombotic thrombocytopenic purpura (iTTP) treatment recommend concurrent therapeutic plasma exchange (TPE), immunosuppressive therapy (IST), and caplacizumab. TPE can complicate antidrug antibody (ADA) measurements by transferring pre-existing antibodies (pre-Abs) into patients via donor plasma and/or diluting treatment-emergent (TE) ADAs.
Objectives: To assess the presence of ADAs in patients with iTTP who received caplacizumab.
Evaluating the potential for iodinated radiocontrast agents to interfere with ADAMTS13 activity testing via fluorescence resonance energy transfer methodology.
Am J Clin Pathol
December 2024
Special Coagulation Laboratory, Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, US.
Objectives: Fluorescence resonance energy transfer (FRET)-based ADAMTS13 activity assays are critical for the diagnosis of thrombotic thrombocytopenic purpura. However, these assays are susceptible to interference. As iodide has been suggested to interfere in laboratory testing via fluorophore quenching or promotion, we aimed to determine whether iodinated contrast (Omnipaque) interferes with the ATS-13 ADAMTS13 Activity Assay 2.
View Article and Find Full Text PDFKinetic modeling of the plasma pharmacokinetic profiles of ADAMTS13 fragment and its Fc-fusion counterpart in mice.
Front Pharmacol
March 2024
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Fusion of the fragment crystallizable (Fc) to protein therapeutics is commonly used to extend the circulation time by enhancing neonatal Fc-receptor (FcRn)-mediated endosomal recycling and slowing renal clearance. This study applied kinetic modeling to gain insights into the cellular processing contributing to the observed pharmacokinetic (PK) differences between the novel recombinant ADAMTS13 fragment (MDTCS) and its Fc-fusion protein (MDTCS-Fc). For MDTCS and MDTCS-Fc, their plasma PK profiles were obtained at two dose levels following intravenous administration of the respective proteins to mice.
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