Identification of high and low responders to allografts.

The immune response to an allograft varies from one individual to another. This individual variation is, at least in part, due to genetic variation in the regulation of cytokine gene expression. High and low cytokine responses in vitro for tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta 1 (TGF-beta1) and other cytokines can be predicted from an individual's cytokine genotype. Using the same genetic markers we have been able to show associations, in particular between TNF-alpha genotype of the recipient and acute allograft rejection and, similarly, between TGF-beta1 genotype and chronic rejection. The ability to identify high and low responders to allografts by a simple genetic test, and to predict who will suffer acute and chronic rejection, has implications for donor selection and recipient treatment as well as for the design and interpretation of clinical trials of new immunosuppressive agents.