Effect of donor-specific transfusions on the outcome of renal allografts in the cyclosporine era

Abstract

Summary Despite the introduction of new immunosuppressive agents, a steady decline of functioning renal allografts after living donation is observed. Thus nonpharmacological strategies to prevent graft loss have to be reconsidered, including donor‐specific transfusions (DST). We introduced a cyclosporine‐based DST protocol for renal allograft recipients from living‐related/unrelated donation. From 1993 to 2003, 200 ml of whole blood, or the respective mononuclear cells from the potential living donor were administered twice to all of our 61 recipient candidates. The transplanted subjects were compared with three groups of patients without DST from the Collaborative Transplant Study (Heidelberg, Germany) during a 6‐year period. Six patients were sensitized without delay for a subsequent cadaveric kidney. DST patients had less often treatment for rejection and graft survival was superior compared with subjects from the other Swiss transplant centers (n = 513) or from Western Europe (n = 7024). To diminish the probability that superior results reflect patient selection rather than effects of DST, a ‘matched‐pair’ analysis controlling for relevant factors of transplant outcome was performed. Again, this analysis indicated that recipients with DST had better outcome. Thus, our observation suggests that DST improve the outcome of living kidney transplants even when modern immunosuppressive drugs are prescribed.

Generation of suppressive blood cells for control of allograft rejection

“…In our setting, in contrast with MMC-induced apoptosis, UV-C apoptotic donor cells accelerated allograft rejection in vivo. It is well known that donor blood prolongs allograft survival [16,[24][25][26]. When we treated blood cells with MMC, their suppressive effect was significantly increased.…”

Siglecs Induce Tolerance to Cell Surface Antigens by BIM-Dependent Deletion of the Antigen-Reactive B Cells

“…This may explain why mHEL cells induced more robust tolerance than mOVA cells, since HEL elicits weak T cell help in C57BL/6J mice(53). In this regard, it is of interest whether dampening T cell help with immunosuppressive drugs or co-stimulatory blockade enhances the effectiveness of DST(9, 54) and tolerance induction with lymphocytes expressing foreign antigen in mice(11, 55). …”

“…These results stimulated the evaluation of donor-specific transfusion (DST) for organ transplantation in humans, with numerous clinical trials reporting a reduced rate of transplant rejection(4-7). Although the success of broad immunosuppressive drugs for transplantation curtailed the use of DST, interest has resurfaced as a result of improved long-term organ survival over treatment with immunosuppressive drugs alone(8, 9). A lack of clear understanding of the cellular mechanism(s) mediating tolerance, however, has hampered the refinement of DST and its adoption for routine use in human transplantation(6, 10).…”

Acquisition of Humoral Transplantation Tolerance upon De Novo Emergence of B Lymphocytes

“…In both these lines of investigation, donor-specific transfusion (DST) seems to be a requirement for improved survival. In addition, a series of clinical and basic studies have previously pointed to the potential utility of DST for improving long-term allograft survival (22)(23)(24). The mechanistic explanation for the beneficial effect of DST has been attributed to a state of "chimerism" (25)(26)(27)(28).…”