Kidney Transplant Rejection Can Be Diagnosed or Even Predicted by Tracking Donor Reactive T Cell Clones in Post-transplant Samples
1Surgery-Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 2Medicine, Nephrology Division, Northwestern University Feinberg School of Medicine, Chicago, IL
Meeting: 2021 American Transplant Congress
Abstract number: 224
Keywords: Kidney transplantation, Non-invasive diagnosis, Rejection, T cell clones
Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes
Session Information
Session Name: Biomarkers, Immune Assessment and Clinical Outcomes - III
Session Type: Rapid Fire Oral Abstract
Date: Monday, June 7, 2021
Session Time: 4:30pm-5:30pm
Presentation Time: 5:05pm-5:10pm
Location: Virtual
*Purpose: To test if kidney transplant (KTx) rejection can be diagnosed by monitoring for donor reactive T-cell (DRTC) clones in post-transplant (post-tx) biopsy and non-invasively in blood and urine samples.
*Methods: From a pre-tx anti-donor MLR assay, the CFSE-diluting CD4 and CD8 DRTCs were flow-sorted and the TcR clonal sequences were identified in them by immunoSEQ® Assay (collectively called TcR-AlloSEQ). The assumption was that TcR-AlloSEQ would identify recipient’s anti-donor T-cell repertoire. Then, in the post-tx period, the presence and abundance of the pre-identified DRTCs were monitored serially in KTx biopsies (3, 12 months and for-cause), blood and urine (3, 6, 12 months and for-cause), again by immunoSEQ.
*Results: This is an interim report on the first 30/80 Standard of Care KTx subjects in a single-center non-randomized prospective study – patients were grouped into stable (n=18), rejecting (n=5) and other causes (n=7) cases. Clones were identified as donor reactive in both CD4 and CD8 subsets from pre-tx MLRs; the DTRCs were mostly from low-frequency clones in the recipient PBMC. DRTCs of both subsets could be detected variably in all post-tx samples. Stable recipients had low DRTCs and rejecting recipients had significantly (p<0.002) elevated DRTCs at months 3 and 6, as well as at rejection, in blood, urine and biopsy (Figure 1). DRTCs increase in each rejecting biopsy suggested that it can be used to diagnose acute rejection. Similar DRTCs increases in blood and urine indicated that rejection diagnosis can also be made non-invasively. Increase in DRTCs observed at 3 months post-Tx predicted biopsy-proven acute rejection that occurred after 3 months in 3/5 patients. Dosage changes of TAC, MMF and prednisone along with the IVIg or belatacept treatment resolved the rejection which also resulted the marked decrease in the presence of DRTCs in the 12-month follow-up samples.
*Conclusions: 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 non-invasively in blood or urine. Completion of the whole study is expected to provide more insights.
To cite this abstract in AMA style:
Sambandam Y, Kandpal M, He J, Huang X, Taylor TS, Shetty AA, Mathew JM, Leventhal JR. Kidney Transplant Rejection Can Be Diagnosed or Even Predicted by Tracking Donor Reactive T Cell Clones in Post-transplant Samples [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/kidney-transplant-rejection-can-be-diagnosed-or-even-predicted-by-tracking-donor-reactive-t-cell-clones-in-post-transplant-samples/. Accessed May 9, 2025.« Back to 2021 American Transplant Congress