Neutrophil Extracellular Traps Aggravate Injury in Complement-Mediated Thrombotic Microangiopathy
Xiao-Tian Liu1,2,3,4, Zi-Xin Hua1,2,3,4, Meng Tan1,2,3,4
1Renal Division, Department of Medicine, Institute of Nephrology, Peking University First Hospital, Peking University, Beijing, China.
Journal of the American Society of Nephrology : JASN
|April 7, 2026
Summary
Neutrophil extracellular traps (NETs) biomarkers are elevated in complement-mediated thrombotic microangiopathy (TMA), driving organ damage by shedding CD59 and activating complement and coagulation pathways.
Area of Science:
- Nephrology
- Immunology
- Hematology
Background:
- Complement hyperactivation and endothelial damage drive organ injury in complement-mediated thrombotic microangiopathy (TMA).
- The role of neutrophil extracellular traps (NETs) in TMA pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of NETs in complement-mediated TMA.
- To examine the impact of NETs on endothelial cells and complement activation.
Main Methods:
- Measured NETs biomarkers in 107 TMA patients and in mice.
- Evaluated the effects of genetic (Pad4 knockout) and pharmacological NETs inhibition (DNase I, GSK484) and neutrophil depletion in TMA mouse models.
- Investigated NETs' influence on membrane attack complex (MAC) and CD59 regulation in human endothelial cells.
Main Results:
- Elevated NETs biomarkers in TMA patients correlated with disease activity and MAC deposition.
- Pad4 knockout, NETs inhibition, and neutrophil depletion attenuated TMA phenotypes and kidney injury in mice.
- NETs induced MAC deposition by promoting CD59 shedding and enhanced coagulation via tissue factor upregulation in endothelial cells.
Conclusions:
- NETs biomarkers are increased in complement-mediated TMA.
- NETs contribute to multi-organ injury by shedding CD59, enhancing complement activation, and promoting coagulation.
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