Abstract: TH-PO0989
Integrated Analysis of T- and B-Cell-Receptor Repertoire in Kidney Recipients
Session Information
- Transplantation: Basic - Immune Biology, Tissue Injury, and Emerging Technologies
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2001 Transplantation: Basic
Authors
- Mueller, Franco B., Weill Cornell Medicine, New York, New York, United States
- Li, Carol Y., Weill Cornell Medicine, New York, New York, United States
- Dadhania, Darshana M., Weill Cornell Medicine, New York, New York, United States
- Suthanthiran, Manikkam, Weill Cornell Medicine, New York, New York, United States
- Muthukumar, Thangamani, Weill Cornell Medicine, New York, New York, United States
Background
We recently reported using RNA sequencing of kidney allografts that chronic-active ABMR (caABMR), but not active-ABMR, resembled T cell mediated rejection (TCMR) molecularly [PMID:38040290]). To further decipher this conundrum, we assessed the TCR and BCR repertoire in kidney allograft biopsies.
Methods
We studied the transcriptomics of 85 kidney biopsies: 17 TCMR, 6 plasma cell-rich acute rejection (PCRR), 7 active-ABMR, 15 CA-ABMR, 6 IFTA, 18 NR, and 16 pre-perfusion (Pre) biopsies. Using the TRUST4 algorithm we reconstructed the immune receptor repertoire in αβ/γδ T cells and B cells from RNA-seq data.
Results
The number of TCR and BCR clonotypes in CA-ABMR and TCMR were similar. Gene set variation analysis (GSVA) score of TCR Signaling and Activation pathway were significantly elevated in TCMR and caABMR compared with NR. However, in TCMR, but not in caABMR, mean TCR clone abundance predicted pathway activation (Fig1), indicating dissociation between infiltrate magnitude and transcriptional output in caABMR.
We further characterized TCR repertoires using rarefaction/extrapolation analysis, top-clone dominance metrics, richness estimation, and rank–abundance distributions. Rank-abundance analysis further demonstrated that TCMR repertoires extend across substantially broader clonotype-rank distributions than caABMR, with preservation of an expanded low-frequency clonotype tail (Fig2).
Conclusion
Our paired TCR and BCR repertoire analysis reveals that despite transcriptional similarities, caABMR and TCMR exhibit distinct functional organization of the adaptive immune response, with pathway activation in TCMR associated with both clonal abundance and repertoire diversity, whereas caABMR is characterized by diversity-associated activation independent of clonal abundance.