Role of the lectin pathway of complement in hematopoietic stem cell transplantation-associated endothelial injury and thrombotic microangiopathy.
Ho, Vincent T
Exp Hematol Oncol
Springer Science and Business Media LLC
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Gavriilaki, E., Ho, V. T., Schwaeble, W., Dudler, T., Daha, M., Fujita, T., & Jodele, S. (2021). Role of the lectin pathway of complement in hematopoietic stem cell transplantation-associated endothelial injury and thrombotic microangiopathy.. Exp Hematol Oncol, 10 (1) https://doi.org/10.1186/s40164-021-00249-8
Funder: omeros corporation
Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a life-threatening syndrome that occurs in adult and pediatric patients after hematopoietic stem cell transplantation. Nonspecific symptoms, heterogeneity within study populations, and variability among current diagnostic criteria contribute to misdiagnosis and underdiagnosis of this syndrome. Hematopoietic stem cell transplantation and associated risk factors precipitate endothelial injury, leading to HSCT-TMA and other endothelial injury syndromes such as hepatic veno-occlusive disease/sinusoidal obstruction syndrome, idiopathic pneumonia syndrome, diffuse alveolar hemorrhage, capillary leak syndrome, and graft-versus-host disease. Endothelial injury can trigger activation of the complement system, promoting inflammation and the development of endothelial injury syndromes, ultimately leading to organ damage and failure. In particular, the lectin pathway of complement is activated by damage-associated molecular patterns (DAMPs) on the surface of injured endothelial cells. Pattern-recognition molecules such as mannose-binding lectin (MBL), collectins, and ficolins-collectively termed lectins-bind to DAMPs on injured host cells, forming activation complexes with MBL-associated serine proteases 1, 2, and 3 (MASP-1, MASP-2, and MASP-3). Activation of the lectin pathway may also trigger the coagulation cascade via MASP-2 cleavage of prothrombin to thrombin. Together, activation of complement and the coagulation cascade lead to a procoagulant state that may result in development of HSCT-TMA. Several complement inhibitors targeting various complement pathways are in clinical trials for the treatment of HSCT-TMA. In this article, we review the role of the complement system in HSCT-TMA pathogenesis, with a focus on the lectin pathway.
Review, Endothelial injury, Complement activation, Lectin pathway, Hematopoietic stem cell transplantation-associated thrombotic microangiopathy
External DOI: https://doi.org/10.1186/s40164-021-00249-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332041