Polymorphisms in immunoregulatory genes: towards individualized immunosuppressive therapy?

In organ transplantation, successful immunosuppression requires that both rejection and infection episodes be minimized. Unfortunately it is currently impossible to predict individual dose requirement for immunosuppressive drugs, but a number of studies of various immune response genes are now being performed with a view to identifying genotypes associated with rejection and/or infection. The key role of cytokines in the immune response and other processes, including fibrosis, has concentrated most of this attention on polymorphisms in cytokine genes. Data on polymorphisms in genes encoding tumor necrosis factor-alpha, transforming growth factor-beta, interferon-gamma and interleukin (IL)-1, 4, 6 and 10 together with the IL-4 receptor have been analyzed but so far there is currently no indication of any consistently positive associations between graft rejection and any of these polymorphisms. Studies of other immunomodulatory genes including the CTLA4 gene and the chemokine receptor CCR-5 have proved more positive though the data, so far, are only preliminary. In conclusion, additional large series studies of these and other cytokine genes, as well as other immunoregulatory gene polymorphisms of proven functional significance are needed to achieve major progress in this area.