ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2025
Limitations of biopsy-based transcript diagnostics to detect T-cell-mediated allograft rejection.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed.
- Biopsy-based Transcriptomics in Banff 2022 Antibody Mediated Rejection Categories.Kidney international reports · 2026Article
- Integrating Tissue Gene Expression Profiling With Histopathology in Pediatric Kidney Recipients.Pediatric transplantation · 2026Article
- Antibody-mediated rejection in ABO-incompatible kidney transplantation.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Article
- Rejection-Focused Precision Medicine in Kidney Transplantation: Biology, Biomarkers, and Artificial Intelligence.Life (Basel, Switzerland) · 2026Review
- Intercenter Variability in the Application of Biopsy-based Transcriptomics in Kidney Transplantation.Transplantation direct · 2025Article
- Renal Allograft Pathology Classifications: Contemporary Updates and Diagnostic Utility.Cureus · 2025Review
- Biopsy-Based Transcriptomics Support Rejection Monitoring Through Repeated Kidney Allograft Biopsies.Kidney international reports · 2025Article
- Additional Diagnoses Other Than Rejection in the Kidney Allograft Biopsy: Pitfalls for Biopsy-based Transcript Diagnostics.Transplantation direct · 2025Article
- Immune Landscape in Kidney Transplantation.Journal of inflammation research · 2025Review
- The Use of Machine Learning in the Diagnosis of Kidney Allograft Rejection: Current Knowledge and Applications.Diagnostics (Basel, Switzerland) · 2024Review
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Abstract
backgroundIsolated tubulitis, borderline changes and isolated arteritis suspicious for histologic T-cell-mediated rejection (hTCMR) remain findings of uncertain significance. Although the Molecular Microscope Diagnostics System (MMDx) has not been trained on those lesions, it was suggested that MMDx might reclassify a subgroup to molecular TCMR (mTCMR).
methodsIn this single-center cohort of 326 consecutive, unselected kidney allograft biopsies assessed by histology and MMDx, we analyzed 249 cases with isolated tubulitis (i0, t1-3, v0; n = 101), borderline changes (according to Banff 2022, v0; n = 9), isolated arteritis (no borderline, v1; n = 37), no inflammation (i0, t0, v0; n = 67) and a positive control cohort (hTCMR, n = 27; mixed histologic rejection, n = 8; both according to Banff 2022; total n = 35). The first three groups were summarized as TCMR-suspicion (n = 147). Subcategorization included the presence and absence of microvascular inflammation (MVI); g+ptc ptc ≥2. Molecular rejection rates and differentiation were investigated.
resultsMolecular rejection rates were 37/147 cases (25.2%; 32 with MVI) in TCMR-suspicion, 6/67 (9%; 4 with MVI) in no inflammation and 30/35 (85.7%; 19 with MVI) in the positive control cohort. Molecular antibody-mediated rejection (mAMR) was present in 39/73 (53.4%) of cases. The presence of donor-specific antibodies at the time of the biopsy was high (127/249, 51%). Only 3 mAMR/TCMR and 0 pure mTCMR cases were detected in TCMR-suspicion and no inflammation, compared with 12 mAMR/TCMR and 10 mTCMR cases in the positive control cohort (P < .001). Even though the TCMR-specific molecular (Classifier) score differentiated between TCMR-suspicion and no inflammation (P = 0.005), rejection phenotype scores (R2 and R3) did not (P = .157 and .121).
conclusionsMMDx did not identify pure mTCMR among isolated tubulitis, borderline changes or isolated arteritis, likely due to low sensitivity for TCMR lesions. However, it identified mAMR or mAMR/TCMR, especially in cases with MVI. Subthreshold findings remain to be further studied.
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