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Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura

(2020) BLOOD. 136(3). p.353-361
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Abstract
Recently, we showed that ADAMTS13 circulates in an open conformation during the acute phase of immune-mediated thrombotic thrombocytopenic purpura (iTTP). Although the cause of this conformational change remains elusive, ADAMTS13 is primarily closed in iTTP patients in remission with ADAMTS13 activity >50% and undetectable anti-ADAMTS13 autoantibodies, as well as after rituximab treatment, suggesting a role for anti-ADAMTS13 autoantibodies. Therefore, immunoglobulin G from 18 acute iTTP patients was purified and added to closed ADAMTS13 in healthy donor plasma. This resulted in open ADAMTS13 in 14 of 18 (78%) samples, proving that anti-ADAMTS13 autoantibodies can induce an open ADAMTS13 conformation. To further elucidate the conformation of ADAMTS13 in iTTP patients, we studied a novel iTTP patient cohort (n = 197) that also included plasma samples from iTTP patients in remission in whom ADAMTS13 activity was <50%. The open ADAMTS13 conformation was found during acute iTTP, as well as in patients in remission with ADAMTS13 activity <50% and in half of the patients with ADAMTS13 activity >50%, although free anti-ADAMTS13 autoantibodies were not always detected. Thus, open ADAMTS13 is a hallmark of acute iTTP, as well as a novel biomarker that can be used to detect subclinical iTTP in patients in remission. Finally, a long-term follow-up study in 1 iTTP patient showed that the open conformation precedes a substantial drop in ADAMTS13 activity. In conclusion, we have shown that anti-ADAMTS13 autoantibodies from iTTP patients induce an open ADAMTS13 conformation. Most importantly, an open ADAMTS13 conformation is a biomarker for subclinical iTTP and could become an important tool in TTP management.
Keywords
Immunology, Cell Biology, Biochemistry, Hematology, VON-WILLEBRAND-FACTOR, FACTOR-CLEAVING PROTEASE, CONFORMATIONAL ACTIVATION, ANTI-ADAMTS13 ANTIBODIES, RELAPSE, REMISSION, AUTOANTIBODIES, PREDICTORS, RITUXIMAB, ANTIGEN

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MLA
Roose, Elien, et al. “Open ADAMTS13, Induced by Antibodies, Is a Biomarker for Subclinical Immune-Mediated Thrombotic Thrombocytopenic Purpura.” BLOOD, vol. 136, no. 3, 2020, pp. 353–61, doi:10.1182/blood.2019004221.
APA
Roose, E., Tellier, A.-S., Tellier, E., Sinkovits, G., Joly, B. S., Dekimpe, C., … Vanhoorelbeke, K. (2020). Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura. BLOOD, 136(3), 353–361. https://doi.org/10.1182/blood.2019004221
Chicago author-date
Roose, Elien, An-Sofie Tellier, Edwige Tellier, György Sinkovits, Bérangère S Joly, Charlotte Dekimpe, Gilles Kaplanski, et al. 2020. “Open ADAMTS13, Induced by Antibodies, Is a Biomarker for Subclinical Immune-Mediated Thrombotic Thrombocytopenic Purpura.” BLOOD 136 (3): 353–61. https://doi.org/10.1182/blood.2019004221.
Chicago author-date (all authors)
Roose, Elien, An-Sofie Tellier, Edwige Tellier, György Sinkovits, Bérangère S Joly, Charlotte Dekimpe, Gilles Kaplanski, Maelle Le Besnerais, Ilaria Mancini, Dr. Tanja Falter, Charis von Auer, Hendrik Feys, Marienn Reti, Heidi Rossmann, Aline Vandenbulcke, Inge Pareyn, Jan Voorberg, Andreas Greinacher, Ygal Benhamou, Hans Deckmyn, Rob R Fijnheer, Zoltan Prohaszka, Flora Peyvandi, Bernhard Lämmle, Paul Coppo, Simon De Meyer, Agnès Veyradier, and Karen Vanhoorelbeke. 2020. “Open ADAMTS13, Induced by Antibodies, Is a Biomarker for Subclinical Immune-Mediated Thrombotic Thrombocytopenic Purpura.” BLOOD 136 (3): 353–361. doi:10.1182/blood.2019004221.
Vancouver
1.
Roose E, Tellier A-S, Tellier E, Sinkovits G, Joly BS, Dekimpe C, et al. Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura. BLOOD. 2020;136(3):353–61.
IEEE
[1]
E. Roose et al., “Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura,” BLOOD, vol. 136, no. 3, pp. 353–361, 2020.
@article{8702415,
  abstract     = {{Recently, we showed that ADAMTS13 circulates in an open conformation during the acute phase of immune-mediated thrombotic thrombocytopenic purpura (iTTP). Although the cause of this conformational change remains elusive, ADAMTS13 is primarily closed in iTTP patients in remission with ADAMTS13 activity >50% and undetectable anti-ADAMTS13 autoantibodies, as well as after rituximab treatment, suggesting a role for anti-ADAMTS13 autoantibodies. Therefore, immunoglobulin G from 18 acute iTTP patients was purified and added to closed ADAMTS13 in healthy donor plasma. This resulted in open ADAMTS13 in 14 of 18 (78%) samples, proving that anti-ADAMTS13 autoantibodies can induce an open ADAMTS13 conformation. To further elucidate the conformation of ADAMTS13 in iTTP patients, we studied a novel iTTP patient cohort (n = 197) that also included plasma samples from iTTP patients in remission in whom ADAMTS13 activity was <50%. The open ADAMTS13 conformation was found during acute iTTP, as well as in patients in remission with ADAMTS13 activity <50% and in half of the patients with ADAMTS13 activity >50%, although free anti-ADAMTS13 autoantibodies were not always detected. Thus, open ADAMTS13 is a hallmark of acute iTTP, as well as a novel biomarker that can be used to detect subclinical iTTP in patients in remission. Finally, a long-term follow-up study in 1 iTTP patient showed that the open conformation precedes a substantial drop in ADAMTS13 activity. In conclusion, we have shown that anti-ADAMTS13 autoantibodies from iTTP patients induce an open ADAMTS13 conformation. Most importantly, an open ADAMTS13 conformation is a biomarker for subclinical iTTP and could become an important tool in TTP management.}},
  author       = {{Roose, Elien and Tellier, An-Sofie and Tellier, Edwige and Sinkovits, György and Joly, Bérangère S and Dekimpe, Charlotte and Kaplanski, Gilles and Le Besnerais, Maelle and Mancini, Ilaria and Falter, Dr. Tanja and von Auer, Charis and Feys, Hendrik and Reti, Marienn and Rossmann, Heidi and Vandenbulcke, Aline and Pareyn, Inge and Voorberg, Jan and Greinacher, Andreas and Benhamou, Ygal and Deckmyn, Hans and Fijnheer, Rob R and Prohaszka, Zoltan and Peyvandi, Flora and Lämmle, Bernhard and Coppo, Paul and De Meyer, Simon and Veyradier, Agnès and Vanhoorelbeke, Karen}},
  issn         = {{0006-4971}},
  journal      = {{BLOOD}},
  keywords     = {{Immunology,Cell Biology,Biochemistry,Hematology,VON-WILLEBRAND-FACTOR,FACTOR-CLEAVING PROTEASE,CONFORMATIONAL ACTIVATION,ANTI-ADAMTS13 ANTIBODIES,RELAPSE,REMISSION,AUTOANTIBODIES,PREDICTORS,RITUXIMAB,ANTIGEN}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{353--361}},
  title        = {{Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura}},
  url          = {{http://dx.doi.org/10.1182/blood.2019004221}},
  volume       = {{136}},
  year         = {{2020}},
}

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