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

Leydi Carolina Velásquez Pereira, Elien Roose, Nuno A. G. Graça, György Sinkovits, Kadri Kangro, Bérangère S. Joly, Edwige Tellier, Gilles Kaplanski, Tanja Falter, Charis Von Auer, et al.
(2021) JOURNAL OF THROMBOSIS AND HAEMOSTASIS. 19(2). p.478-488
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Abstract
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.
Keywords
Hematology, ADAMTS13, autoantibodies, epitope mapping, immunophenotyping, thrombotic thrombocytopenic purpura, VON-WILLEBRAND-FACTOR, FACTOR-CLEAVING PROTEASE, BINDING-SITE, ANTIBODIES, AUTOANTIBODIES, CONTAINS, SURFACE

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MLA
Velásquez Pereira, Leydi Carolina, et al. “Immunogenic Hotspots in the Spacer Domain of ADAMTS13 in Immune‐mediated Thrombotic Thrombocytopenic Purpura.” JOURNAL OF THROMBOSIS AND HAEMOSTASIS, vol. 19, no. 2, 2021, pp. 478–88, doi:10.1111/jth.15170.
APA
Velásquez Pereira, L. C., Roose, E., Graça, N. A. G., Sinkovits, G., Kangro, K., Joly, B. S., … Vanhoorelbeke, K. (2021). Immunogenic hotspots in the spacer domain of ADAMTS13 in immune‐mediated thrombotic thrombocytopenic purpura. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 19(2), 478–488. https://doi.org/10.1111/jth.15170
Chicago author-date
Velásquez Pereira, Leydi Carolina, Elien Roose, Nuno A. G. Graça, György Sinkovits, Kadri Kangro, Bérangère S. Joly, Edwige Tellier, et al. 2021. “Immunogenic Hotspots in the Spacer Domain of ADAMTS13 in Immune‐mediated Thrombotic Thrombocytopenic Purpura.” JOURNAL OF THROMBOSIS AND HAEMOSTASIS 19 (2): 478–88. https://doi.org/10.1111/jth.15170.
Chicago author-date (all authors)
Velásquez Pereira, Leydi Carolina, Elien Roose, Nuno A. G. Graça, György Sinkovits, Kadri Kangro, Bérangère S. Joly, Edwige Tellier, Gilles Kaplanski, Tanja Falter, Charis Von Auer, Heidi Rossmann, Hendrik Feys, Marienn Reti, Zoltán Prohászka, Bernhard Lämmle, Jan Voorberg, Paul Coppo, Agnès Veyradier, Simon F. De Meyer, Andres Männik, and Karen Vanhoorelbeke. 2021. “Immunogenic Hotspots in the Spacer Domain of ADAMTS13 in Immune‐mediated Thrombotic Thrombocytopenic Purpura.” JOURNAL OF THROMBOSIS AND HAEMOSTASIS 19 (2): 478–488. doi:10.1111/jth.15170.
Vancouver
1.
Velásquez Pereira LC, Roose E, Graça NAG, Sinkovits G, Kangro K, Joly BS, et al. Immunogenic hotspots in the spacer domain of ADAMTS13 in immune‐mediated thrombotic thrombocytopenic purpura. JOURNAL OF THROMBOSIS AND HAEMOSTASIS. 2021;19(2):478–88.
IEEE
[1]
L. C. Velásquez Pereira et al., “Immunogenic hotspots in the spacer domain of ADAMTS13 in immune‐mediated thrombotic thrombocytopenic purpura,” JOURNAL OF THROMBOSIS AND HAEMOSTASIS, vol. 19, no. 2, pp. 478–488, 2021.
@article{8702419,
  abstract     = {{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.}},
  author       = {{Velásquez Pereira, Leydi Carolina and Roose, Elien and Graça, Nuno A. G. and Sinkovits, György and Kangro, Kadri and Joly, Bérangère S. and Tellier, Edwige and Kaplanski, Gilles and Falter, Tanja and Von Auer, Charis and Rossmann, Heidi and Feys, Hendrik and Reti, Marienn and Prohászka, Zoltán and Lämmle, Bernhard and Voorberg, Jan and Coppo, Paul and Veyradier, Agnès and De Meyer, Simon F. and Männik, Andres and Vanhoorelbeke, Karen}},
  issn         = {{1538-7933}},
  journal      = {{JOURNAL OF THROMBOSIS AND HAEMOSTASIS}},
  keywords     = {{Hematology,ADAMTS13,autoantibodies,epitope mapping,immunophenotyping,thrombotic thrombocytopenic purpura,VON-WILLEBRAND-FACTOR,FACTOR-CLEAVING PROTEASE,BINDING-SITE,ANTIBODIES,AUTOANTIBODIES,CONTAINS,SURFACE}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{478--488}},
  title        = {{Immunogenic hotspots in the spacer domain of ADAMTS13 in immune‐mediated thrombotic thrombocytopenic purpura}},
  url          = {{http://doi.org/10.1111/jth.15170}},
  volume       = {{19}},
  year         = {{2021}},
}
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