A novel monoclonal antibody against the von Willebrand Factor A2 domain reduces its cleavage by ADAMTS13.
We developed a novel murine monoclonal antibody (mAb) against the C-terminal α-helix of the human von Willebrand factor A2, designated SZ-179. We showed that SZ-179 inhibited the interactions between VWF and ADAMTS13 and prevented the degradation of high molecular weight VWF multimers. Importantly, SZ-179 reduced the proteolysis of VWF-R1597W mutant by rADAMTS13 dose-dependently under native conditions. Our findings reveal a potential therapeutic target for bleeding disorders.
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.
Lulu
L
Zhang
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.
Jian
J
Su
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.
Fei
F
Shen
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.
Zhenni
Z
Ma
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.
Yiming
Y
Zhao
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.
Lijun
L
Xia
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China. ruanchanggeng@suda.edu.cn.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China. ruanchanggeng@suda.edu.cn.
Changgeng
0000-0001-8821-5679
C
Ruan
D000071120:ADAMTS13 Protein / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000915:Antibody Affinity; D006801:Humans; D006825:Hybridomas; D000072417:Protein Domains / Q000276:immunology; D011994:Recombinant Proteins / Q000378:metabolism; D014841:von Willebrand Factor / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
ADAMTS13; Monoclonal antibody; von Willebrand factor