Acute T-cell mediated rejection (TCMR) occurs when the body’s T-cells react against the transplanted organ due to differences in certain protein markers (HLA) between the donor and the recipient. This reaction often leads to problems with the transplanted organ, sometimes resulting in its loss.

This affects around 30% of kidney and simultaneous kidney-pancreas (SPK) transplant recipients within the first-year post-transplant. It can be detected either when patients show signs of dysfunction in the transplant or during routine biopsy checks even when there are no apparent issues with the transplant.

Our collaborative research has revealed that even minor grades of TCMR, in borderline cases or in those without evident symptoms, can predict future problems, with the transplanted organ. Additionally, incomplete resolution of acute TCMR can progress into a more chronic form, further damaging the organ. Acute TCMR can also trigger the production of antibodies that attack the transplanted organ, leading to additional complications such as antibody mediated rejection.

Standard treatment for acute TCMR involves high doses of steroids given intravenously followed by a tapering dose taken by mouth. However, a significant number of patients treated this way still have ongoing rejection. This unresolved rejection has been linked to higher risks of losing the transplanted organ. Currently the optimal steroid dose for acute TCMR is unknown, which may lead to under- or overdosing of steroids with its associated side effects.

To improve long-term outcomes for transplant recipients, it is crucial to completely resolve acute TCMR to prevent the activation of chronic inflammatory processes that can irreversibly damage the organ. There is a lot of interest in finding new treatments for TCMR, such as using medications to block specific proteins involved in the immune response. But before these new treatments can be tested, we need to establish the best steroid treatment dosing to define dosing with care.