Thorac Cardiovasc Surg 2012; 60 - PP141
DOI: 10.1055/s-0031-1297788

Using skin transplants as early in vivo indicators for graft rejection in heart transplantation

U Arunagirinathan 1, M Stubbendorff 1, T Deuse 1, 2, X Hua 1, J Velden 3, F Haddad 2, RC Robbins 2, H Reichenspurner 1, S Schrepfer 1, 2
  • 1University Heart Center Hamburg, TSI-Lab, Hamburg, Germany
  • 2Stanford University, CT Surgery, Stanford, United States
  • 3University Hospital of Hamburg-Eppendorf, Pathology, Hamburg, Germany

Aims: The early detection of graft rejection is pivotal in the management of patients with heart transplants. Since presently a valid non-invasive early indicator for graft rejection is lacking, we investigated the use of skin transplants as early in vivo indicators for heart rejection when simultaneously transplanted in a rat model.

Methods: Heterotopic heart and skin transplantations were performed from firefly luciferase (Fluc) expressing Lewis into Brown Norway rats (group1; n=12). Group 2 (n=12) received only heart transplants. After 5 days, 6 animals from each group were recovered and the systemic cellular immune response was assessed using the Enzyme Linked Immune Spot Technique (ELISPOT). The heart grafts were histologically graded according to the ISHLT-classification and systemic donor-specific antibodies were determined using Fluorescence-Activated Cell Sorting (FACS). Rejection of skin grafts of the remaining animals (n=6) were monitored by bioluminescence imaging (BLI) and correlated to the beating scores of their heart transplants.

Results: Skin cells undergoing rejection could be identified using the novel BLI technique, since the detected light signal is ATP dependent. The BLI signal of skin grafts dropped after 4.7±0.8 days, whereas cessation of the heart beating was on day 12.8±1.9. The IFN-γ spot frequency as determined via ELISPOT was 499±288 in group 1, compared to 253±117 in group 2 (p=0.003), indicating a higher systemic immune response in animals receiving simultaneously heart and skin grafts from the same donor. However, no significant differences in heart beating score were identified between group1 and 2. Indeed, the ISHLT classifications of transplanted hearts were also similar in both groups (between 2 and 3A), as well as the donor-specific antibodies (group 1: 13.5±2.1 and group 2: 19.6±7.3; p=n.s.).

Conclusions: Changes in skin grafts can be observed and interpreted as early signs of the systemic activated immune system. Therefore, skin transplants can be used as external non invasive in vivo indicators for graft rejection in heart transplantation, when transplanted simultaneously from the same donor.