"Inventors have isolated a single-domain antibody (designated KB-VWF-D3.1) targeting the A3-domain, the epitope of which overlaps the collagen-binding site. Binding of KB-VWF-D3.1 proved independent of VWF multimer size. However, its interaction with VWF was lost upon proteolysis by ADAMTS13, suggesting that proteolysis in the A2-domain modulates exposure of its epitope in the A3-domain. Inventors therefore used KB-VWF-D3.1 to monitor VWF degradation in plasma samples. Spiking experiments showed that a loss of 10% intact-VWF could be detected using this single-domain antibody. By comparing plasma from volunteers to that of congenital VWD-patients, intact-VWF levels were significantly reduced for all VWD-types, and most severely in VWD-type 2A(IIA) in which mutations promote ADAMTS13- mediated proteolysis. Unexpectedly, low-grade proteolysis in VWD-type 1 and -type 2M was also observed. Thus, this single-domain antibody proved sensitive to detect low-grade degradation in plasma from patients with AVWS and congenital VWD, including types 1 and 2M.
The present invention relates to an isolated single domain antibody targeting at least one region of A3-domain of VWF, wherein the region comprising the following sequences: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and/or SEQ ID NO: 4. "