ArticleBlood2021
N-glycan-mediated shielding of ADAMTS13 prevents binding of pathogenic autoantibodies in immune-mediated TTP.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Molecular Dynamics Simulations with NAMD and Trajectory Analysis.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Trp1250, Lys1252, and Arg1367 of ADAMTS13 comprise a hot spot for anti-CUB domain antibodies in patients with iTTP.Blood advances · 2025Article
- N-glycan shielded CUB domains of ADAMTS13 prevent binding of C-terminal antibodies in patients with immune-mediated TTP.Blood advances · 2025Article
- Agents of shield: glycans mask antibody epitopes on ADAMTS13.Blood advances · 2025Article
- Structural bioinformatics for rational drug design.Research and practice in thrombosis and haemostasis · 2025Article
- N-Glycan Insertion for Probing Protein-Protein Interactions and Epitope Mapping.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Mechanisms of inhibition of human monoclonal antibodies in immune thrombotic thrombocytopenic purpura.Blood · 2023Article
- Frontiers in pathophysiology and management of thrombotic thrombocytopenic purpura.International journal of hematology · 2023Review
- Syntaxin 5 determines Weibel-Palade body size and von Willebrand factor secretion by controlling Golgi architecture.Haematologica · 2022Article
- TTP: From empiricism for an enigmatic disease to targeted molecular therapies.British journal of haematology · 2022Review
- The standard of care for immune thrombotic thrombocytopenic purpura today.Journal of thrombosis and haemostasis : JTH · 2021Review
- Autoantibody-resistant ADAMTS13 variant.Blood · 2021Article
Corrections and comments
- Commented on by
Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is an autoimmune disorder caused by the development of autoantibodies targeting different domains of ADAMTS13. Profiling studies have shown that residues R568, F592, R660, Y661, and Y665 within exosite-3 of the spacer domain provide an immunodominant region of ADAMTS13 for pathogenic autoantibodies that develop in patients with iTTP. Modification of these 5 core residues with the goal of reducing autoantibody binding revealed a significant tradeoff between autoantibody resistance and proteolytic activity. Here, we employed structural bioinformatics to identify a larger epitope landscape on the ADAMTS13 spacer domain. Models of spacer-antibody complexes predicted that residues R568, L591, F592, K608, M609, R636, L637, R639, R660, Y661, Y665, and L668 contribute to an expanded epitope within the spacer domain. Based on bioinformatics-guided predictions, we designed a panel of N-glycan insertions in this expanded epitope to reduce the binding of spacer domain autoantibodies. One N-glycan variant (NGLY3-ADAMTS13, containing a K608N substitution) showed strongly reduced reactivity with TTP patient sera (28%) as compared with WT-ADAMTS13 (100%). Insertion of an N-glycan at amino acid position 608 did not interfere with processing of von Willebrand factor, positioning the resulting NGLY3-ADAMTS13 variant as a potential novel therapeutic option for treatment of iTTP.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.