N-Acetyl-L-Cysteine Potentially Inhibits Complement Activation in Transplantation-Associated Thrombotic Microangiopathy

Jiaqian Qi; Shuhong Hu; Xuefeng He; Tingting Pan; Liping Yang; Rui Zhang; Yaqiong Tang; Depei Wu; Yue Han

doi:10.1016/j.jtct.2021.12.018

N-Acetyl-L-Cysteine Potentially Inhibits Complement Activation in Transplantation-Associated Thrombotic Microangiopathy

Transplant Cell Ther. 2022 Apr;28(4):216.e1-216.e5. doi: 10.1016/j.jtct.2021.12.018. Epub 2021 Dec 31.

Authors

Jiaqian Qi¹, Shuhong Hu², Xuefeng He², Tingting Pan¹, Liping Yang¹, Rui Zhang¹, Yaqiong Tang¹, Depei Wu³, Yue Han⁴

Affiliations

¹ National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China.
² National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
³ National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China. Electronic address: [email protected].
⁴ National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China. Electronic address: [email protected].

PMID: 34979328
DOI: 10.1016/j.jtct.2021.12.018

Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA) has a high mortality rate and lacks effective treatments. We searched the GEO database and analyzed RNA-seq data and whole-genome sequencing data from patients' blood samples. We identified N-acetyl-L-cysteine (NAC) as a possible therapeutic target for TA-TMA. In vitro experiments showed that NAC reduced complement activation and VWF multimerization in HUVECs. We also treated a 36-year-old female TA-TMA patient with NAC. Hemoglobin, platelet counts, lactate dehydrogenase levels, and sC5b-9 levels and schistocytes were normalized after using NAC. It shows that NAC may be an effective drug to improve TA-TMA symptoms by inhibiting complement activation.

Keywords: Complement system; N-acetyl-L-cysteine; Transplantation associated-thrombotic micro-angiopathy.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Acetylcysteine / pharmacology
Adult
Complement Activation
Female
Hematopoietic Stem Cell Transplantation*
Humans
Thrombotic Microangiopathies* / drug therapy
Treatment Outcome

Substances

Acetylcysteine