Abstract: FR-PO1176
Kidney Biopsy Inflammatory Phenotype Differentiates T-Cell-Mediated Rejection (CMR) from Polyomavirus Nephropathy (PVN)
Session Information
- Transplantation: Clinical - Rejection, Biomarkers, and Pharmacology
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Leong, Matthew, Cedars-Sinai Medical Center, Los Angeles, California, United States
- Huang, Edmund, Cedars-Sinai Medical Center, Los Angeles, California, United States
- Nast, Cynthia C., Cedars-Sinai Medical Center, Los Angeles, California, United States
Background
Differentiating PVN from CMR is a challenge in kidney transplant pathology. This is critical for appropriate therapy but problematic, as both encompass tubulointerstitial inflammation.
Methods
6 kidney biopsies each of CMR and PVN were stained for SV40 followed by destaining and multiplex immunofluorescence analysis with 36 markers for immune cell phenotype and tubule segment (PT, DT, CD) identification using the Lunaphore COMET system. SV40 stained and matched multiplex OME-TIFF images were analyzed using whole-slide registration workflow with segmentation of SV40+ nuclei, and of multiplex OME-TIFF cells assigned immune phenotypes and tubular segment. Immune cells were spatially assigned to each tubule using centroid-to-mask distances and summarized within the tubular wall band, 0-20 um peritubular cuff, and additional peritubular distance rings. Final summaries compared immune-cell composition, wall involvement, cuffing, T-cell subsets, B cells, and plasma-like cells across tubule classes and SV40 status.
Results
Banff scores were CMR IB, 2A and 2B; PVN 2 and 3. Comparing peritubular infiltrates in CMR vs SV40- tubule areas of PVN, CMR showed denser CD8+, CD4+ and myeloid cells, with raw tubule-level p-values of p<0.001, p<0.001, and p=0.018, respectively across PT and CD. Major T-cell subset differences involved CD4 KI67+, CD8 KI67+, CD8 TOX+/GZMB+, and CD8 KI67+TOX+/GZMB+ cells around PT and CD. Peri-DT areas skewed to CD8+ cells while CD areas had CD8+ cycling/cytotoxic and CD4+ memory/activation-associated cells. CMR tubulitis had more cycling CD4+, CD8+ and NK cells. Compared to CMR, PVN infiltrates skewed to activated-memory/exhaustion-like T-cells, especially CD4-M4 PD1+/TOX+ activated-memory and CD8 PD1+/CD45RO+ activated-memory cells with lower cycling/cytotoxic cells. SV40+ vs SV40- tubular areas were enriched for virus-associated T-cell remodeling and CD8 KI67+ cells focused on CD with a trend to more B cells.
Conclusion
This study shows compartmental spatial/tubule-associated interstitial inflammatory patterns differentiating CMR vs PVN. CMR has more diffuse cycling and cytotoxic T-cell subsets and myeloid cells. PVN shows more memory-associated states in SV40- areas with T-cell remodeling around SV40+ tubules. These findings support a unique CMR inflammatory phenotype distinct from PVN, showing promise for distinguishing these lesions when they co-occur.
Funding
- Clinical Revenue Support