Purpose of review
To summarize the current knowledge regarding mechanisms linking the complement system to transplant injury, highlighting findings reported since 2013.
Building upon the documentation that complement activation is a pathogenic mediator of posttransplant ischemia-reperfusion injury, emerging evidence from animal models indicates that blocking either the classical or lectin pathways attenuates ischemia-reperfusion injury. Immune cell-derived and locally activated complement, including intracellular C3, positively modulates alloreactive T-cell activation and expansion, whereby simultaneously inhibiting regulatory T-cell induction and function, and together promoting transplant rejection. Although alloantibody-initiated complement activation directly injures target cells, complement-dependent signals activate endothelial cells to facilitate T-cell-dependent inflammation. Complement activation within allografts contributes to progressive chronic injury and fibrosis.
The complement cascade, traditionally considered to be relevant to transplantation only as an effector mechanism of antibody-initiated allograft injury, is now understood to damage the allograft through multiple mechanisms. Complement activation promotes posttransplant ischemia-reperfusion injury, formation and function of alloantibody, differentiation and function of alloreactive T cells, and contributes to chronic progressive allograft failure. The recognition that complement affects transplant injury at many levels provides a foundation for targeting complement as a therapy to prolong transplant survival and improve patient health.