Method for Assessing Inhibition Kinetics of Autoantibodies Against ADAMTS13 in Immune-Mediated Thrombotic Thrombocytopenic Purpura.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy caused by autoantibodies directed against ADAMTS13, a plasma metalloenzyme that cleaves von Willebrand factor (VWF). The autoantibodies are primarily IgG types, and patients typically present with multiple antibodies that are specific to various regions of the protein. Mechanistically, many questions remain regarding exactly how these antibodies modulate ADAMTS13 to lead to the inhibition of its activity. Investigating enzyme kinetics and how the presence of autoantibodies affects these parameters can reveal important insights into the mechanism(s) underlying the antibody-mediated inhibition of ADAMTS13. As the antibodies are central to the pathology of iTTP, gaining a deeper understanding of their effects may lead to the development of targeted therapeutic agents to treat the disease that could potentially be more effective for these patients. Here, we describe a way to analyze the inhibitory kinetics of autoantibodies in the context of iTTP.