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Ferrata Storti Foundation
Haematologica 2019 Volume 104(6):1268-1276
Hemostasis
Generation of anti-idiotypic antibodies to detect anti-spacer antibody idiotopes in acute thrombotic thrombocytopenic purpura patients
An-Sofie Schelpe,1 Elien Roose,1 Bérangère S. Joly,2,3 Inge Pareyn,1 Ilaria Mancini,4,5 Marina Biganzoli,4,5 Hans Deckmyn,1 Jan Voorberg,6 Rob Fijnheer,7 Flora Peyvandi,4,5 Simon F. De Meyer,1 Paul Coppo,8 Agnès Veyradier2,3 and Karen Vanhoorelbeke1
1
Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak
Kortrijk, Belgium; 2Service d’Hématologie Biologique, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, France; 3EA3518, Institut Universitaire d’Hématologie Saint- Louis, Université Paris Diderot, France; 4Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Italy; 5Department of Pathophysiology and Transplantation, Fondazione Luigi Villa, Milan, Italy; 6Department of Molecular and Cellular Hemostasis, Sanquin-AMC Landsteiner Laboratory, Amsterdam, the Netherlands; 7Department of Internal Medicine, Meander Medical Center, Amersfoort, the Netherlands and 8Sorbonne Universités, Service d'Hématologie et Centre de Référence des Microangiopathies Thrombotiques (CNR-MAT), Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, France
ABSTRACT
In autoantibody-mediated autoimmune diseases, autoantibody profiling allows patients to be stratified and links autoantibodies with disease severity and outcome. However, in immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients, stratification according to anti- body profiles and their clinical relevance has not been fully explored. We aimed to develop a new type of autoantibody profiling assay for iTTP based on the use of anti-idiotypic antibodies. Anti-idiotypic antibodies against 3 anti-spacer autoantibodies were generated in mice and were used to capture the respective anti-spacer idiotopes from 151 acute iTTP plasma samples. We next deciphered these anti-spacer idiotope profiles in iTTP patients and investigated whether these limited idiotope profiles could be linked with disease severity. We developed 3 anti-idiotypic antibodies that recognized particular idiotopes in the anti-spacer autoantibodies II-1, TTP73 or I-9, that are involved in ADAMTS13 binding; 35%, 24% and 42% of patients were positive for antibodies with the II-1, TTP73 and I-9 idiotopes, respectively. Stratifying patients according to the corresponding 8 anti-spacer idiotope profiles provided a new insight into the anti-spacer II-1, TTP73 and I-9 idiotope profiles in these patients. Finally, these limited idiotope profiles showed no association with disease severity. We success- fully developed 3 anti-idiotypic antibodies that allowed us to determine the profiles of the anti-spacer II-1, TTP73 and I-9 idiotopes in iTTP patients. Increasing the number of patients and/or future development of additional anti-idiotypic antibodies against other anti-ADAMTS13 autoantibodies might allow idiotope profiles of clinical, prognostic value to be identified.
Introduction
In autoantibody-mediated autoimmune diseases, patients develop autoantibod- ies against self-antigens.1 The autoantibody response can be directed to multiple self-antigens like in systemic sclerosis,2 Sjögren syndrome,3 and type 1 diabetes4 or to a single self-antigen like myasthenia gravis5 and Graves disease.6 Patients suffer- ing from the autoimmune disorder immune-mediated thrombotic thrombocy- topenic purpura (iTTP) present with an autoantibody response against one antigen: the von Willebrand factor (VWF) cleaving protease ADAMTS13 (A Disintegrin And
Correspondence:
KAREN VANHOORELBEKE
Karen.Vanhoorelbeke@kuleuven.be
Received: September 6, 2018. Accepted: November 30, 2018. Pre-published: December 6, 2018.
doi:10.3324/haematol.2018.205666
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