A novel biomarker to improve the quality of life of immune mediatied thrombotic thrombocytopenic purpura patients.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening autoimmune disorder caused by an autoantibody induced severe deficiency of the blood metalloprotease ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats, member 13; ADAMTS13 activity < 10%). The disease course of iTTP patients is characterized by three different types of phases: an acute phase, a remission phase and a relapse phase (in about 40% of the iTTP patients). Currently, a three-monthly monitoring of the ADAMTS13 activity is used to follow-up iTTP patients. However, ADAMTS13 activity is not a good biomarker to predict relapse in these patients, since iTTP patients can live for years with a decreased ADAMTS13 activity without the reappearance of clinical signs. Therefore, a novel biomarkers to better predict relapse and to identify when ADAMTS13 activity monitoring needs to be intensified are urgently needed.

ADAMTS13 is a multidomain enzyme, which can adopt a closed or open ADAMTS13 conformation, through interaction between the spacer (S) and CUB domains. We recently showed that ADAMTS13 adopts an open conformation in iTTP patients in acute phase. In contrast, ADAMTS13 conformation is closed in healthy donors, Hemolytic uremic syndrome patients (HUS), sepsis patients and non-immune mediated TTP patients. In addition, we could show that anti-ADAMTS13 autoantibodies are the factor which opens ADAMTS13 in iTTP patients. Hence we identified open ADAMTS13 as a novel biomarker for the diagnosis of iTTP.

In this study, we want to evaluate “open ADAMTS13” as a predictor for relapse, which could aid identifying patients with a need for an intensified monitoring. Additionally, to improve a correct and rapid diagnosis of iTTP, we will develop the “open ADAMTS13” assay on the easy- to-use innovative fiber-optic surface plasmon resonance (FO-SPR) platform of FOx Biosystems, which will become available in a broad range of hospitals.