Karen Vanhoorelbeke, Belgium

KU Leuven Campus Kulak Kortrijk Laboratory for Thrombosis Research
The research of Prof. Dr. Karen Vanhoorelbeke focuses on the molecular mechanisms by which the hemostatic proteins van Willebrand factor (VWF) and its cleaving enzyme ADAMTS13 contribute to health and disease in particular in the autoimmune disorder thrombotic thrombocytopenic purpura (https://thrombosis.kuleuven-kulak.be). Her research is embedded in several national and international research projects. Recently she was awarded a Horizon2020 Marie Curie training network grant ‘PROFILE’ of which she is the coordinator (http://www.itn-profile.eu). She is author and coauthor of more than 165 scientific publications in international peer reviewed journals and is (co) promotor of 32 PhD students.

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OPEN ADAMTS13 CONFORMATION, INDUCED BY AUTOANTIBODIES, IS A BIOMARKER FOR SUBCLINICAL IMMUNE-MEDIATED THROMBOTIC THROMBOCYTOPENIC PURPURA

Session Name
PS09 - NOVEL AUTOANTIBODIES RECEPTORS AUTOIMMUNE DYSAUTONOMIA
Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
13:30 - 15:30
Room
HALL C
Lecture Time
14:50 - 15:00
Presenter
Session Icon
Pre Recorded

Abstract

Background and Aims

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is caused by autoantibodies against the blood enzyme ADAMTS13. We showed that patients with acute iTTP have an open ADAMTS13 conformation, while healthy donors (HD) and 78% of iTTP patients in remission with a normal ADAMTS13 activity (TS13:act; >50%) have a closed ADAMTS13. However, the cause of the open ADAMTS13 conformation, as well as the ADAMTS13 conformation in iTTP patients in remission with TS13:act <50% is unknown. Therefore, we investigated whether anti-ADAMTS13 autoantibodies induce conformational changes in ADAMTS13 and also determined the ADAMTS13 conformation in iTTP patients in remission with TS13:act <50%.

Methods

Purified IgG’s from 18 acute iTTP samples were added to folded ADAMTS13 from HD and tested for ADAMTS13 conformation. Additionally, ADAMTS13 conformation was determined in 166 iTTP samples from remission phase.

Results

Closed ADAMTS13 in HD plasma was opened by addition of purified IgGs from 14 of the 18 (78%) acute iTTP plasmas, demonstrating that patient anti-ADAMTS13 autoantibodies can induce a conformational change in ADAMTS13. Further, ADAMTS13 was closed in 62% (56/91) of the remission samples with TS13:act >50%, confirming our previous results. Interestingly, ADAMTS13 was open in 95% (71/75) of remission samples with TS13:act <50%.

Conclusions

We showed that anti-ADAMTS13 autoantibodies cause a conformational change in ADAMTS13 in iTTP. Additionally, we found that besides acute iTTP patients, also the majority (106/166) of iTTP patients in remission have an open ADAMTS13 conformation, indicating that the underlying pathophysiology is still ongoing. Therefore open ADAMTS13 could be used as a biomarker for subclinical disease during iTTP monitoring.

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