Individualized immunosuppression after transplantation. New insights into pathogenesis and treatment of graft arteriosclerosis
While major improvements have been made in the prevention and treatment of acute transplant rejection, accelerated cardiac allograft vasculopathy (CAV) still limits the long-term success of heart transplantation (HTx). This session gave us an outstanding overview concerning new experimental models, stem cell and immune pathways as well as on new treatment options with respect to CAV.
In the first presentation, Q. Xu (London, GB) demonstrated that (based on mouse models for vein grafts and CAV) stem cells identified in blood and bone marrow, as well as the vasculature, contribute to allograft atherosclerotic lesion formation. Moreover, he described that the alloimmune response induces chemokines that attract stem cells to the allograft.
In the second presentation, A.G. Pockley (Sheffield, GB) indicated that extracellular stress proteins (like gp96) have immunostimulatory and immunosuppressive potential depending on the context in which they are encountered by the cellular immune-response network. He described that high dose gp96 treatment prolongs survival in animal transplant models, at least in part via modulation of T-cell function.
In the third presentation, B. de Geest (Leuven, BE) described that human apoA-I gene transfer increases the number of circulating EPCs, enhances their incorporation into allografts, promotes endothelial regeneration, and attenuates neointima formation in a murine model of transplant arteriosclerosis. In addition, he showed that the HDL-induced effect on EPC migration depends on the receptor SRBI.
Finally, S. Kofler (Munich, Germany) presented the current and future potential of immunosuppressive drugs and pointed out that individualized immunosuppression is needed. Calcineurin-inhibitor free protocols and the use of new costimulatory signal inhibitors are currently being studied.
Conclusion
Alloimmune-dependent and alloimmune-independent injuries in the context of impaired/ heightened repair mechanisms (reduced activity of endothelial cell progenitors, enhanced smooth muscle cell progenitors) are controlling the progression of graft arteriosclerosis. As individual responses to an allograft change over time, we need to develop assays for monitoring the recipient immune response as well as individualized methods for therapeutic immune modulation. The era of using standardized immunosuppressive protocols is over; immune tolerance appears on the horizon.
Notes to editor
This congress report accompanies a presentation given at the ESC Congress 2008. Written by the author himself/herself, this report does not necessarily reflect the opinion of the European Society of Cardiology.
The content of this article reflects the personal opinion of the
author/s and is not necessarily the official position of the
European Society of Cardiology.