Korean J Transplant.  2022 Nov;36(Supple 1):S116. 10.4285/ATW2022.F-2354.

Reduced ceramides are associated with acute rejection in liver transplant patients and skin and hepatocyte transplant mice

• Kim N
• Yoo HJ
• Kang Y
• Kim SJ
• Yoon YI
• Lee Y
• Tak E
• Kim JJ
• Hwang S
• Jung DH

• KMID: 2535632
• DOI: http://doi.org/10.4285/ATW2022.F-2354

Abstract

We set up this study to discover novel metabolic biomarkers for acute rejection and understand the roles of ceramides on im-mune cells in acute rejection. Serum concentrations of ceramides and sphingomyelins were measured by LC-MS/MS. Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplant (LT) recipients with than without acute rejection (AR). Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. To understand the underlying mecha-nisms, a ceramide synthase inhibitor, fumonisin B1, was administered to reduce ceramide levels during mixed lymphocyte re-actions (MLR) and in mice given skin grafts. Fumonisin B1 exacerbated allogeneic immune responses in vitro and in vivo, partly changing the subsets of plasmacytoid dendritic cells in the draining lymph nodes. The results of MLR with ceranib-2, an inhib-itor of ceramidase, and C24 ceramide also support that increasing ceramide concentrations could benefit transplant recipients with AR.