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