The Development of Assays
Development of new tests
In order to implement novel tolerance induction protocols in the clinic, we need to develop diagnostic tests which can identify (in a retrospective or prospective manner) those patients in whom tolerance can be, or has been, successfully induced.
Even in well-defined experimental models, tolerance induction is rarely successful 100% of the time. In humans, the extended immunological experience of transplant recipients before transplantation (i.e. heterologous immunity leading to an increased memory lymphocyte pool, including donor-reactive memory T cells), the frequent use of pre-injured organs from elderly and brain-dead donors (resulting in enhanced immunogenicity and incidence of chronic rejection) and the development of post-transplant infections all influence the risk of acute and chronic transplant rejection and probably the threshold for tolerance induction as well.
In this context, establishing immunological and molecular profiles which can predict the success or failure of tolerance induction is a priority for the project . The major purpose of such tests would be to minimise the risk of novel tolerance inducing principles and immunosuppression weaning during clinical trials of tolerance induction.
Assays have been developed for the:
•· definition of immunological pre-transplant constellations identifying patients that are not suitable for a particular tolerance induction protocol (definition of high-risk patients before transplantation).
•· early identification of failure of tolerance induction, possibly before graft deterioration occurs (definition of negative predictors early after transplantation).
•· early demonstration of tolerance after induction therapy (definition of early positive predictors of success after transplantation)
•· harmful injury/tolerisation of the anti-microbial immune response (definition of safety markers).
•· Identification of tolerance state markers in long term stable recipients under immunosuppressive therapy.
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