Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 52-59 |
| Number of pages | 8 |
| Journal | Current Transplantation Reports |
| Volume | 6 |
| Issue number | 1 |
| DOIs | |
| State | Published - 15 Mar 2019 |
Keywords
- Allograft inflammation
- Antibody-mediated rejection
- Complement
- Ischemia reperfusion injury
- T cell activation