You are here: Symposia and Workshops Past ROTRF Symposia and Workshops ROTRF Early Morning Workshop, Sydney 2008
Mechanisms of Graft Rejection and Acceptance: Pathways to a New Clinical Era
Antibody-Mediated Rejection: The Next Frontier
Philip F. Halloran, University of Alberta, Edmonton, Canada
For decades, monitoring of immune response and closely related biomarkers has been used to detect or predict graft rejection. Such immunomonitoring includes measurement of parameters that can be determined pre-transplant (such as MHC matching) or post-transplant (such as analysis of anti-donor antibodies). Decades of active research in this field have, however, generated few useful early markers of outcome. More recently, a better control of the recipient's immune response and the recognition of nephrotoxicity and other side effects of immunosuppressive drugs as the foremost burden for transplant recipients have partially shifted monitoring towards the assessment of immunological risk. A new field of research is emerging devoted to the detection of markers of operational tolerance (or very low risk) in the absence of markers of rejection.
It has been reported that about 25% of liver recipients become tolerant following interruption of immunosuppressive drugs. The proportion of transplant recipients with long-term stable kidney graft function who could enjoy a state of “operational tolerance” upon progressive immunosuppressive drugs weaning is currently unknown. Biomarkers may help in the design of “intelligent” immunosuppression minimisation and ultimately withdrawal procedures, and in the identification of kidney transplant recipient patients in whom such procedures may be beneficial. Different strategies for identifying clinical and biological markers of long-term outcome will be summarised. The way in which composite markers of “operational tolerance” or high rejection risk “see” a cohort of 200 kidney transplant recipients with stable and well-functioning grafts four years post-transplantation will be described. The data indicate that these patients are heterogeneous for a number of parameters, potentially enabling further selection of patients in whom weaning of immunosuppression may potentially be safer. The characteristics of this cohort of patients will be discussed in terms of how to develop clinical study protocols that may help to answer a key question emerging in transplantation, namely whether we can safely interrupt immunosuppression in some kidney recipients.