ArticleResearch and practice in thrombosis and haemostasis2020
Generation and validation of small ADAMTS13 fragments for epitope mapping of anti-ADAMTS13 autoantibodies in immune-mediated thrombotic thrombocytopenic purpura.
Article in Research and practice in thrombosis and haemostasis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Novel cryptic ADAMTS13 epitopes uncover a distinct open ADAMTS13 conformation in immune-mediated TTP.Haematologica · 2026Article
- Open or closed? Understanding the molecular mechanisms and clinical implications of ADAMTS13's conformation.HemaSphere · 2025Review
- Unraveling antibody-induced structural dynamics in the ADAMTS13 CUB1-2 domains via HDX-MS.Blood advances · 2025Article
- ADAMTS13 and Non-ADAMTS13 Biomarkers in Immune-Mediated Thrombotic Thrombocytopenic Purpura.Journal of clinical medicine · 2023Review
- Mechanisms of inhibition of human monoclonal antibodies in immune thrombotic thrombocytopenic purpura.Blood · 2023Article
- ADAMTS13 conformation and immunoprofiles in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura.Blood advances · 2023Article
- Anti-cysteine/spacer antibodies that open ADAMTS13 are a common feature in iTTP.Blood advances · 2021Article
- Anti-ADAMTS13 autoantibody profiling in patients with immune-mediated thrombotic thrombocytopenic purpura.Blood advances · 2021Article
- Erratum.Research and practice in thrombosis and haemostasis · 2021Article
- Generation and validation of small ADAMTS13 fragments for epitope mapping of anti-ADAMTS13 autoantibodies in immune-mediated thrombotic thrombocytopenic purpura.Research and practice in thrombosis and haemostasis · 2020Article
Corrections and comments
- Erratum issuedErratum.2021
Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn immune-mediated thrombotic thrombocytopenic purpura (iTTP), patients develop an immune response against the multidomain enzyme ADAMTS13. ADAMTS13 consists of a metalloprotease (M) and disintegrin-like (D) domain, 8 thrombospondin type 1 repeats (T1-T8), a cysteine-rich (C), a spacer (S), and 2 CUB domains (CUB1-2). Previous epitope mapping studies have used relatively large overlapping ADAMTS13 fragments.
objectivesWe aimed at developing small nonoverlapping ADAMTS13 fragments to fine map anti-ADAMTS13 autoantibodies in iTTP patients.
methodsA library of 16 ADAMTS13 fragments, comprising several small (M, DT, C, S, T2-T5, T6-T8, CUB1, CUB2), and some larger fragments with overlapping domains (MDT, MDTC, DTC, CS, T2-T8, CUB1-2, MDTCS, T2-C2), were generated. All fragments, and ADAMTS13, were expressed as a fusion protein with albumin domain 1, and purified. The folding of the fragments was tested using 17 anti-ADAMTS13 monoclonal antibodies with known epitopes. An epitope mapping assay using small ADAMTS13 fragments was set up, and validated by analyzing 18 iTTP patient samples.
resultsValidation with the monoclonal antibodies demonstrated that single S and CUB1 were not correctly folded, and therefore CS and CUB1-2 fragments were selected instead of single C, S, CUB1, and CUB2 fragments. Epitope mapping of antibodies of patients with iTTP confirmed that 6 nonoverlapping ADAMTS13 fragments M, DT, CS, T2-T5, T6-T8, and CUB1-2 were sufficient to accurately determine the antibody-binding sites.
conclusionWe have developed a tool to profile patients with iTTP according to their anti-ADAMTS13 antibodies for a better insight in their immune response.
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