In most transplant programs, long-term transplant recipients tend to be treated with similar immunosuppressive protocols. However, such uniform treatment may lead to complications from overimmunosuppression in some and underimmunosuppression in others. Previous studies of withdrawal of one immunosuppressive drug have not been successful. An important question is whether an individual immune parameter test or a battery of these tests would best predict long-term graft outcome in stable patients. Retrospective data from individual laboratories has suggested that immune parameters (donor antigen-specific hyporeactivity and allogeneic microchimerism) predict successful long-term outcome after solid organ transplantation. However, each of these parameters has only been applied to a subpopulation of transplant recipients. This grant will focus on the potential use of these two immunologic parameters to predict long-term graft success in a broad transplant population. We will determine whether donor antigen-specific hyporeactivity o the helper pathway (Specific Aim 1), and peripheral blood allogeneic microchimerism (Specific Aim 2), correlate with improved long-term graft outcome. We will perform a prospective study, testing these two immune parameters for, liver and kidney recipients transplanted at Duke University Medical Center and University of Minnesota. Both universities have long-established mechanisms for clinical follow-up and clinical data collection. We will evaluate the usefulness of these immune parameters in each organ group. We will determine whether, perhaps in specific organ groups one parameter can be used in lieu of another. At the same time our multicenter approach will allow us to test large numbers of recipients; we will be able to accumulate data on sufficient numbers of recipients to test the null hypothesis. successful, we subsequently plan to use these immune parameters to determine if immunosuppression can be individualized. If so, by selectively lowering immunosuppression in some recipients but maintaining it in others, we will provide significant long-term savings (cost, morbidity, and outcome improvement) for solid organ transplant recipients.
| Jackson, A; Palmer, S; Davis, R D et al. (2001) Cytokine genotypes in kidney, heart, and lung recipients: consequences for acute and chronic rejection. Transplant Proc 33:489-90 |
