Journal article
Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura
- Roose, Elien ORCID KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
- Schelpe, An-Sofie ORCID KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
- Tellier, Edwige C2VN INSERM 1263, MARSEILLE, France
- Sinkovits, György ORCID Semmelweis University, Budapest, Hungary
- Joly, Bérangère S Hôpital Lariboisière - Assistance Publique Hôpitaux de Paris, PARIS, France
- Dekimpe, Charlotte KU Leuven Kulak, Zwevegem, Belgium
- Kaplanski, Gilles Aix Marseille Univ, INSERM, INRA, C2VN, France
- Le Besnerais, Maelle Rouen University Hospital, Rouen, France
- Mancini, Ilaria ORCID Department of Pathophysiology and Transplantation, Università degli Studi di Milano, and Fondazione Luigi Villa, Milan, Idaho, Italy
- Falter, Dr. Tanja University Medical Center Mainz, Mainz, Germany
- von Auer, Charis Mainz University Hospital, Mainz, Germany
- Feys, Hendrik Benoit ORCID Ghent University, Belgium
- Reti, Marienn Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Szent Laszlo Hospital Campus, Budapest, Hungary
- Rossmann, Heidi University Medical Center Mainz, Mainz, Germany
- Vandenbulcke, Aline KU Leuven campus Kortrijk, Kortrijk, Belgium
- Pareyn, Inge KULeuven campus Kortrijk, Kortrijk, Belgium
- Voorberg, Jan Sanquin Research Amsterdam UMC Landsteiner Laboratory, Amsterdam, Netherlands
- Greinacher, Andreas ORCID University Medicine Greifswald, Greifswald, Germany
- Benhamou, Ygal Service de médecine interne, Normandie université, UniRouen, U1096, 76000 Rouen, France., ROUEN, France
- Deckmyn, Hans ORCID IRC, KU Leuven Campus Kortrijk, Kortrijk, Belgium
- Fijnheer, Rob R University Hospital Utrecht, Utrecht, Netherlands
- Prohaszka, Zoltan Semmelweis University, Budapest, Hungary
- Peyvandi, Flora ORCID Università degli Studi di Milano, Milan, Italy
- Lämmle, Bernhard ORCID Bern University Hospital, Switzerland
- Coppo, Paul AP-HP.SU, Paris, France
- De Meyer, Simon KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
- Veyradier, Agnès Hôpital Lariboisière, PARIS, France
- Vanhoorelbeke, Karen ORCID KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
- 2020-4-30
Published in:
- Blood. - American Society of Hematology. - 2020
English
Recently, we showed that during the acute phase of immune-mediated thrombotic thrombocytopenic purpura (iTTP), ADAMTS13 circulates in an open conformation. Although the cause of this conformational change in acute iTTP remains elusive, ADAMTS13 is mainly closed in iTTP patients (i) in remission with an ADAMTS13 activity >50% and undetectable anti-ADAMTS13 autoantibodies, and (ii) after rituximab treatment, suggesting a role for anti-ADAMTS13 autoantibodies. Therefore, IgGs from 18 acute iTTP patients were purified and added to closed ADAMTS13 in healthy donor plasma. This resulted in open ADAMTS13 in 14/18 (78%) samples, proving that indeed 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 of iTTP patients in remission where ADAMTS13 activity was <50%. The open ADAMTS13 conformation was not only found during acute iTTP but also in patients in remission with an ADAMTS13 activity <50% and in half of the patients with an ADAMTS13 activity >50%, although free anti-ADAMTS13 autoantibodies were not always detected. Thus open ADAMTS13 is not only a hallmark of acute iTTP, but also a novel biomarker to detect subclinical iTTP in patients in remission. Finally, a long term follow-up study in one iTTP patient showed that the open conformation precedes a severe 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.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1182/blood.2019004221
- ISSN 0006-4971
- Persistent URL
- https://sonar.ch/global/documents/28401
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