Donor Reactive T-Cell Clones to Diagnose and Predict Rejection

American Transplant Congress 2021

In a virtual presentation at the American Transplant Congress 2021, Y. Sambandam and colleagues reported interim results of a single-center, nonrandomized prospective study designed to test the hypothesis that kidney transplant rejection can be diagnosed by monitoring for donor reactive T-cell (DRTC) clones in a post-transplant biopsy and noninvasively in blood and urine samples. The presentation was titled Kidney Transplant Rejection Can Be Diagnosed or Even Predicted by Tracking Donor Reactive T-cell Clones in Post-Transplant Samples.

From a pretransplant anti-donor mixed lymphocyte reaction (MLR) assay, CFSE-diluting CD4 and CD8 DRTCs were flow-sorted and immunoSEQ® Assay was used to identify the T-cell receptor (TcR) clonal sequences (collectively called TcR-AlloSEQ). The premise was that TcR-AlloSEQ would identify the recipient’s anti-donor T-cells.

During the post-transplant period, the presence and abundance of the pre-identified DRTCs were serially monitored via immunoSEQ in kidney transplant biopsies at 3 and 12 months, and for cause, as well as in blood and urine samples at 3, 6, and 12 months and for cause.

In results of 30 of 80 standard of care kidney transplant recipients, patients were categorized as stable (n=18), rejecting (n=5), and other causes (n=7). Clones were identified as donor reactive in both CD4 and CD8 subsets from pretransplant MLR; the DTRCs were primarily from low-frequency clones in the recipient peripheral blood mononuclear cell.

DRTCs of both subsets could be detected variably in all post-transplant samples. Recipients in the stable group had low DRTCs and those in the rejecting group had significantly (P<.002) elevated DRTCs at months 3 and 6, and rejection in biopsy, and in blood and urine sample tests. The increase in each rejecting biopsy suggested possible use in acute rejection diagnosis.  The increases in the blood and urine samples also suggested that rejection diagnosis is possible noninvasively.

The 3-month post-transplant observation of increase in DRTCs was a predictor of biopsy-proven acute rejection in three of five patients. The rejection was resolved via dosage changes of tacrolimus, mycophenolate mofetil, and prednisone along with intravenous immunoglobulin or belatacept treatment. The dosage changes also resulted in a marked decrease in the presence of DRTCs in samples at 12-months of follow-up.

In conclusion, the researchers said, “These interim results suggested that monitoring for DRTCs can diagnose an ongoing rejection and can even predict an upcoming rejection and that this can be achieved noninvasively in blood or urine. Completion of the whole study is expected to provide more insights.”

Source: Sambandam Y, Kandpal M, He J, et al. Kidney transplant rejection can be diagnosed or even predicted by tracking donor reactive T cell clones in post-transplant samples. Abstract of a presentation at the virtual American Transplant Congress 2021 (abstract #224), June 7, 2021.