PB0309 - Immunoprofiles and open ADAMTS13 in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Kazuya SAKAI, MD, PhD

Dr.
Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk
8500, West-Vlaanderen, Belgium

Co-Author(s)

MM

Masanori Matsumoto

Professor
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan
Kashihara, Nara, Japan
LD

Laure De Waele

PhD student
Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
Kortrijk, West-Vlaanderen, Belgium
CD

Charlotte Dekimpe

Post-Doc
Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
Kortrijk, West-Vlaanderen, Belgium
CT

Claudia Tersteeg

Prof., Dr.
Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
Kortrijk, West-Vlaanderen, Belgium
SD

Simon F. De Meyer

Prof., Dr., Eng.
Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
Kortrijk, West-Vlaanderen, Belgium
Eriko Hamada, MD

PhD student
Nara Medical University
Kashihara, Nara, Japan
MK

Masayuki Kubo

Medical staff
Department of Blood Transfusion Medicine, Nara Medical University
Kashihara, Nara, Japan
Karen Vanhoorelbeke, PhD

Prof., Dr.
Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
Kortrijk, West-Vlaanderen, Belgium

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is caused by an autoantibody (autoAb) induced ADAMTS13 deficiency. Immunoprofiles of anti-ADAMTS13 autoAbs have been well-studied in mainly the Caucasian population. In the same population, ADAMTS13 with an open conformation was identified as a novel biomarker for iTTP. However, this information is not available for other ethnic cohorts.

Aims: To study the immunoprofile of anti-ADAMTS13 autoAbs and the presence of open ADAMTS13 in a Japanese cohort of acute iTTP patients.

Methods: Immunoprofiling was performed on citrated plasma samples of 195 Japanese iTTP patients in ELISA using M, DT, CS, T2-T5, T6-T8 and CUB domains. The open conformation of ADAMTS13 was studied in ELISA using monoclonal Ab 1C4 which recognizes a cryptic epitope in the S domain of ADAMTS13.

Results: In the Japanese cohort, anti-CS autoAbs were present in 73.0%, anti-T2-5 in 53.5%, anti-CUB in 51.8%, anti-T6-8 in 45.9%, anti-M in 25.8% and anti-DT autoAbs in 22.6% of the patients. We identified 28 different immunoprofiles of which only one was dominant, the one characterized by only CS autoAbs (in 28.8% of the patients). When comparing the 3 most prevalent profiles with the other profiles, the former were linked with better clinical outcome. Finally, in 77 of the 195 samples enough ADAMTS13 antigen was present to determine the ADAMTS13 conformation, which was open in 74 of the patients (96%).

Conclusion(s): The immunoprofile with only-anti-CS autoAbs was the most common immunoprofile in the Japanese iTTP cohort while 3 dominant profiles were identified in the Caucasian cohort. Whether the differences in the prevalence and types of the other immunoprofiles between cohorts is related to ethnic background remains to be determined. Validation of open ADAMTS13 as a common biomarker in iTTP in the Japanese cohort further supports the use of this biomarker in the diagnosis of iTTP.