Figure 3. Emerging therapies to inhibit HLA antibody–induced allograft injury.

Emerging therapies for AMR include upstream complement inhibition with C1 esterase (C1-INH) or antibody against C1s. DSAs are capable of cross-linking HLA molecules on the donor endothelial and smooth muscle cells, resulting in activation of the mTOR signaling axis. Rapamycin (sirolimus) and other rapalogs (everolimus) inhibit mTOR and may dampen vascular cell growth and fibrosis, which contributes to chronic rejection. Finally, abolishing Fc-dependent antibody effector functions through cleavage of the Fc region with IdeS, or removal of the N-linked glycan with EndoS, is likely to hamper activation of the classical complement cascade as well as prevent interactions with FcγRs on monocytes, neutrophils, and NK cells.