Co-inhibition of immunoproteasome subunits LMP2 and LMP7 enables prevention of transplant arteriosclerosis.

So far, effective pharmacological agents to treat transplant arteriosclerosis and ensuing chronic allograft rejection are lacking. Co-inhibition, but neither individual inhibition, of peptidolytically active immunoproteasome LMP7 and/nor LMP2 subunits using epoxyketone inhibitors significantly prevents transplant arteriosclerosis by suppressing T cell-mediated and humoral immune rejection. LMP7 and LMP2 are identified as targets for the prevention of chronic immune rejection after transplantation. Pharmaceuticals that co-inhibit immunoproteasome subunits are currently clinically tested as drugs against autoimmunity. These drugs hold great promise for suppressing transplant arteriosclerosis and allograft rejection, potentially improving prognosis of patients after solid organ transplantation.