Child‐onset thrombotic thrombocytopenic purpura caused by p.R498C and p.G259PfsX133 mutations in ADAMTS13

Schelpe, An‐Sofie; Orlando, Christelle; Ercig, Bogac; Geeroms, Chloë; Pareyn, Inge; Vandeputte, Nele; Pereira, Leydi Carolina Velásquez; Roose, Elien; Fostier, Karel; Nicolaes, Gerry A. F.; Deckmyn, Hans; Meyer, Simon F. De; Vanhoorelbeke, Karen; Jochmans, Kristin

doi:10.1111/ejh.13094

Cited by 5 publications

(7 citation statements)

References 45 publications

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“…First, we compared two autoantibody assays in which rADAMTS-13 was coated but the detection antibodies were different (Table 1, set-up 2 and 3). In our reference ELISA (Table 1, set-up 2), HRP-labeled polyclonal goat anti-human IgG antibodies are used, whereas a combination of four HRP-labeled monoclonal mouse anti-human IgG 1-4 antibodies is used in the other ELISA 13,14 (Table 1, set-up 3). Correlation between autoantibody levels measured using these two ELISAs was only moderate (P = .0028, r = .66; Figure 1A).…”

Section: Re Sults and Discussionmentioning

confidence: 99%

“…11,12 To detect anti-ADAMTS-13 IgGs, polyclonal anti-human IgG antibodies 10 or a mixture of monoclonal anti-human IgG 1-4 antibodies are used. 13,14 However, these different ELISA methods have not been compared side by side and the influence on the anti-ADAMTS-13 autoantibody titers is not known. Therefore, we assessed the influence of different rADAMTS-13 presentation-and autoantibody detection approaches in ELISA.…”

Section: Introductionmentioning

confidence: 99%

“…This might result in a different ADAMTS‐13 conformation and thereby a different autoantibody binding 11,12 . To detect anti‐ADAMTS‐13 IgGs, polyclonal anti‐human IgG antibodies 10 or a mixture of monoclonal anti‐human IgG 1–4 antibodies are used 13,14 . However, these different ELISA methods have not been compared side by side and the influence on the anti‐ADAMTS‐13 autoantibody titers is not known.…”

Section: Introductionmentioning

confidence: 99%

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Determination of anti‐ADAMTS‐13 autoantibody titers in ELISA: Influence of ADAMTS‐13 presentation and autoantibody detection

Dekimpe

Roose

Kangro

et al. 2021

Journal of Thrombosis and Haemostasis

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Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is caused by inhibitory and/or clearing anti-ADAMTS-13 (A Disintegrin and Metalloprotease with ThromboSpondin type 1 repeats, member 13) autoantibodies. To determine the presence and total level of anti-ADAMTS-13 autoantibodies, commercial and in-house developed ELISAs are performed. However, different ELISA methods vary in relation to the presentation of recombinant (r)ADAMTS-13 and the detection method of the anti-ADAMTS-13 autoantibodies. Currently, the influence of those different approaches on anti-ADAMTS-13 autoantibody titers is not known. Objectives:To assess the influence of different ADAMTS-13 presentation-and autoantibody detection methods on anti-ADAMTS-13 autoantibody titers in ELISA.Materials/Methods: Anti-ADAMTS-13 autoantibody titers from 18 iTTP patients were determined using four different set-ups of anti-ADAMTS-13 autoantibody ELISAs. The ELISAs varied in the used presentation of rADAMTS-13 (directly coated full-length rADAMTS-13, directly coated rMDTCS and rT2C2, or antibody-captured full-length rADAMTS-13) and the detection antibodies (polyclonal anti-human IgG or monoclonal anti-human IgG 1-4 antibodies).Results: Strong correlations between the different anti-ADAMTS-13 autoantibody ELISA approaches were observed, when using polyclonal anti-human IgG detection antibodies recognizing all IgG subclasses similarly, independent of the method of rADAMTS-13 presentation. Anti-ADAMTS-13 autoantibody titers correlated less when using a mixture of monoclonal anti-human IgG 1-4 , because not all IgG subclasses were recognized with similar affinities. Conclusion:Anti-ADAMTS-13 autoantibody levels using different methods of rADAMTS-13 presentation strongly correlate. However, the levels of anti-ADAMTS-13

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Section: Re Sults and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Determination of anti‐ADAMTS‐13 autoantibody titers in ELISA: Influence of ADAMTS‐13 presentation and autoantibody detection

Dekimpe

Roose

Kangro

et al. 2021

Journal of Thrombosis and Haemostasis

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“…We used monoclonal anti-ADAMTS13 antibodies: 3H9 (anti-metalloprotease domain); [27][28][29][30][31] 19H4 (anti-thrombospondin type-1 repeat 8 domain); [27][28][29][30] 17G2 (anti-CUB1 domain); [27][28][29][30] and 3E4, 32 15D1, 32 I-9 33 and II-1 (all anti-spacer domain). 33 See supporting information for details.…”

Section: Monoclonal Anti-adamts13 Antibodiesmentioning

confidence: 99%

“…Expression and concentration determination: Full-length WT ADAMTS13 and spacer hybrids were expressed in CHOEBNALT85 cells (European Patent EP1851319B1, Icosagen Cell factory OÜ, Kambja, Estonia), analyzed by western blot, and the concentration quantified in cell culture medium using our in-house developed ADAMTS13 antigen ELISA. 27,29,30 See supporting information for details.…”

Section: Generation Of Full-length Wild Type (Wt) Adamts13 and Spacmentioning

confidence: 99%

Immunogenic hotspots in the spacer domain of ADAMTS13 in immune‐mediated thrombotic thrombocytopenic purpura

Pereira

Roose

Graça

et al. 2021

Journal of Thrombosis and Haemostasis

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Background Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is caused by anti‐ADAMTS13 autoantibodies inducing a severe deficiency of ADAMTS13. Epitope mapping studies on samples obtained during acute iTTP episodes have shown that the iTTP immune response is polyclonal, with almost all patients having autoantibodies targeting the spacer domain of ADAMTS13. Objectives To identify the immunogenic hotspots in the spacer domain of ADAMTS13. Patients/methods A library of 11 full‐length ADAMTS13 spacer hybrids was created in which amino acid regions of the spacer domain of ADAMTS13 were exchanged by the corresponding region of the spacer domain of ADAMTS1. Next, the full‐length ADAMTS13 spacer hybrids were used in enzyme‐linked immunosorbent assay to epitope map anti‐spacer autoantibodies in 138 samples from acute and remission iTTP patients. Results Sixteen different anti‐spacer autoantibody profiles were identified with a similar distribution in acute and remission patients. There was no association between the anti‐spacer autoantibody profiles and disease severity. Almost all iTTP samples contained anti‐spacer autoantibodies against the following three regions: amino acid residues 588‐592, 602‐610, and 657‐666 (hybrids E, G, and M). Between 31% and 57% of the samples had anti‐spacer autoantibodies against amino acid regions 572‐579, 629‐638, 667‐676 (hybrids C, J, and N). In contrast, none of the samples had anti‐spacer autoantibodies against amino acid regions 556‐563, 564‐571, 649‐656, and 677‐685 (hybrids A, B, L, and O). Conclusion We identified three hotspot regions (amino acid regions 588‐592, 602‐610, and 657‐666) in the spacer domain of ADAMTS13 that are targeted by anti‐spacer autoantibodies found in a large cohort of iTTP patients.

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In vitro characterization of a novel Arg102 mutation in the ADAMTS13 metalloprotease domain

Waele

Vermeersch

Nguyen

et al. 2023

Journal of Thrombosis and Haemostasis

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Child‐onset thrombotic thrombocytopenic purpura caused by p.R498C and p.G259PfsX133 mutations in ADAMTS13

Abstract: The ADAMTS13 mutations result in a severe ADAMTS13 deficiency explaining the patient's phenotype.

Cited by 5 publications

References 45 publications

Determination of anti‐ADAMTS‐13 autoantibody titers in ELISA: Influence of ADAMTS‐13 presentation and autoantibody detection

Determination of anti‐ADAMTS‐13 autoantibody titers in ELISA: Influence of ADAMTS‐13 presentation and autoantibody detection

Immunogenic hotspots in the spacer domain of ADAMTS13 in immune‐mediated thrombotic thrombocytopenic purpura

In vitro characterization of a novel Arg102 mutation in the ADAMTS13 metalloprotease domain

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