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A human monoclonal antibody against the distal carboxyl terminus of ADAMTS-13 modulates its susceptibility to an inhibitor in thrombotic thrombocytopenic purpura.

Konstantine HalkidisDon L SiegelX Long Zheng
Published in: Journal of thrombosis and haemostasis : JTH (2021)
Our results demonstrate for the first time that a human monoclonal antibody fragment, the single chain fragment of the variable region (scFv) isolated from a patient with acute iTTP that binds the distal carboxyl-terminus of ADAMTS-13, is able to activate ADAMTS-13 and increase the proteolytic cleavage of a FRETS-VWF73 substrate; moreover, binding of such a human monoclonal antibody against the carboxyl-terminus of ADAMTS-13 to plasma ADAMTS-13 appears to modulate inhibition by another human monoclonal antibody (i.e., scFv4-20), also isolated from an iTTP patient, that targets the spacer domain of ADAMTS-13. These results provide new insights into our understanding of the pathogenesis of iTTP.
Keyphrases
  • monoclonal antibody
  • endothelial cells
  • pluripotent stem cells
  • intensive care unit
  • acute respiratory distress syndrome