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Complement activation and kidney transplantation; a complex relationship

Lookup NU author(s): Dr Beth Gibson, Chloe Connelly, Dr Salta Moldakhmetova, Professor Neil SheerinORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Although kidney transplantation is the best treatment for end stage kidney disease, the benefits are limited by factors such as the short fall in donor numbers, the burden of immunosuppression and graft failure. Although there have been improvements in one-year outcomes, the annual rate of graft loss beyond the first year has not significantly improved, despite better therapies to control the alloimmune response. There is therefore a need to develop alternative strategies to limit kidney injury at all stages along the transplant pathway and so improve graft survival. Complement is primarily part of the innate immune system, but is also known to enhance the adaptive immune response. There is increasing evidence that complement activation occurs at many stages during transplantation and can have deleterious effects on graft outcome. Complement activation begins in the donor and occurs again on reperfusion following a period of ischemia. Complement can contribute to the development of the alloimmune response and may directly contribute to graft injury during acute and chronic allograft rejection. The complexity of the relationship between complement activation and allograft outcome is further increased by the capacity of the allograft to synthesise complement proteins, the contribution complement makes to interstitial fibrosis and complement’s role in the development of recurrent disease. The better we understand the role played by complement in kidney transplant pathology the better placed we will be to intervene. This is particularly relevant with the rapid development of complement therapeutics which can now target different the different pathways of the complement system. Combining our basic understanding of complement biology with preclinical and observational data will allow the development and delivery of clinical trials which have best chance to identify any benefit of complement inhibition.

Publication metadata

Author(s): Gibson B, Connelly C, Moldakhmetova S, Sheerin NS

Publication type: Article

Publication status: Published

Journal: Immunobiology

Year: 2023

Volume: 228

Issue: 4

Print publication date: 01/07/2023

Online publication date: 02/06/2023

Acceptance date: 15/05/2023

Date deposited: 07/06/2023

ISSN (print): 0171-2985

ISSN (electronic): 1878-3279

Publisher: Elsevier GmbH


DOI: 10.1016/j.imbio.2023.152396


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