Role of Complement Activation in Allograft Inflammation

Purpose of Review Novel paradigms have broadened our understanding of mechanisms through which complement mediates allograft inflammation/injury. Herein, we review advances in the field and highlight therapeutic implications. Recent Findings Pre-clinical and translational human trials have elucidated complement-dependent mechanisms of post-transplant ischemia-reperfusion (I/R) injury. Immune cell-derived, and intracellular, complement activation is newly linked to proinflammatory T cell immunity relevant to allograft rejection. Complement-induced immune regulation, including C5a ligation of C5a receptor 2 on T cells, C5a/C5a receptor 1 interactions on regulatory myeloid cells, and C1q binding to CD8 + T cells, can inhibit proinflammatory T cells and/or prolong murine allograft survival. Pilot trials of complement inhibition to treat/prevent human I/R- or antibody-initiated allograft injury show promise. Summary The complement system participates in allograft injury through multiple context-dependent mechanisms involving various components and receptors. These new insights along with development and implementation of individualized complement inhibitory strategies have potential to improve transplant outcomes.