ArticleJournal of thrombosis and haemostasis : JTH2021
Phage display broadly identifies inhibitor-reactive regions in von Willebrand factor.
Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Deep mutational scanning and massively parallel kinetics of plasminogen activator inhibitor-1 functional stability to probe its latency transition.The Journal of biological chemistry · 2022Article
- Article
- Deep mutational scanning of the plasminogen activator inhibitor-1 functional landscape.Scientific reports · 2021Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCorrection of von Willebrand factor (VWF) deficiency with replacement products containing VWF can lead to the development of anti-VWF alloantibodies (i.e., VWF inhibitors) in patients with severe von Willebrand disease (VWD).
objectiveLocate inhibitor-reactive regions within VWF using phage display.
methodsWe screened a phage library displaying random, overlapping fragments covering the full-length VWF protein sequence for binding to a commercial anti-VWF antibody or to immunoglobulins from three type 3 VWD patients who developed VWF inhibitors in response to treatment with plasma-derived VWF. Immunoreactive phage clones were identified and quantified by next-generation DNA sequencing (NGS).
resultsNext-generation DNA sequencing markedly increased the number of phages analyzed for locating immunoreactive regions within VWF following a single round of selection and identified regions not recognized in previous reports using standard phage display methods. Extending this approach to characterize VWF inhibitors from three type 3 VWD patients (including two siblings homozygous for the same VWF gene deletion) revealed patterns of immunoreactivity distinct from the commercial antibody and between unrelated patients, though with notable areas of overlap. Alloantibody reactivity against the VWF propeptide is consistent with incomplete removal of the propeptide from plasma-derived VWF replacement products.
conclusionThese results demonstrate the utility of phage display and NGS to characterize diverse anti-VWF antibody reactivities.
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