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. 2020 Mar 24;21(6):2245. doi: 10.3390/ijms21062245

Table 1.

Transcriptome analysis on indication biopsies with borderline changes-histological category and different controls. ABMR, antibody-mediated rejection; TCMR, T-cell mediated rejection; BL, borderline changes; PBTs, pathogenesis-based transcripts; CATs, infiltration of cytotoxic T cells; GRIT1, interferon-gamma and rejection induced transcripts; KT, kidney parenchymal transcripts; IFTA, interstitial fibrosis and tubular atrophy; AKI, acute kidney injury; BL, borderline changes.

Reference Time & Type of Biopsy Sample Size Methods & Results Main Conclusion
Mueller TF et al. Clinical indication Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays ABMR and TCMR manifested similar PBT disturbances. Biopsies with minimal PBT disturbances had a very low incidence of rejection.
Am J Transplant 2007 [35] N = 143. ↑ CAT1, CAT2, GRIT1, GRIT2;
↓ KT1-KT2 in TCMR GRIT1 associated with C4d staining (ABMR)
De Freitas DG et al. Clinical indication Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays Most cases designated borderline by histopathology are found to be non-rejection by molecular phenotyping.
Am J Transplant 2011 [42] TCMR(n = 35), BL (n = 45), non-rejection (n = 116) Molecular changes measured according to T-cell burden; a rejection classifier; a canonical TCMR classifier; and the risk score. Reassigned borderline biopsies as TCMR like 13/40 (33%) or non-rejection-like 27/40 (67%).
Decision tree analysis showed that i-total >27% and tubulitis extent > 3% match the molecular diagnosis of TCMR in 85% of cases.
Halloran PF et al. Clinical indication Affymetrix microarrays. The molecular TCMR score has potential to add new insight, particularly in situations where histology is ambiguous or potentially misleading.
Am J Transplant 2013 [43] International Collaborative Microarray Study (n = 300). Microarray expression files for BFC403 (GSE36059) and INT300 (GSE48581) cohorts. TCMR scores divided into high or low using the same cut off of 0.1.
TCMR (n = 32), BL (n = 46)
Hrubá P et al. BL early clinical biopsies (n = 13) and 3-month protocol biopsies (n = 15) Illumina microarray analysis. Variations in gene expression between clinical and subclinical borderline changes despite similar histological findings.
Kidney Int 2017 [45] ↑ C19orf59, CXCL2, IL6, S100A8, S100A9, FGA in early clinical biopsies as compared to protocol biopsies
↑ SAA1, CLEC5A, FGA in borderline biopsies with IFTA progression
Halloran PF et al. Clinical indication Affymetrix hgu219 PrimeView microarray chips. MMDx would add valuable support for clinical decisions beyond current standard-of care.
Am J Transplant 2017 [44] International Collaborative Microarray Study (n = 519). Molecular classifier scores (ABMRpm [positive ≥0.20], TCMRt [positive ≥0.10], Rejection [positive ≥0.30])
ABMR (n = 88), ABMR suspected (n = 10), TCMR (n = 29), AKI (n = 43), BL (n = 31), atrophy/fibrosis (n = 84), “no abnormalities” (n = 141).
Reeve J et al. Clinical indication. 13 centres (n = 1208) Affymetrix hgu219 PrimeView microarray chips. Borderline changes are classified as no rejection (72%), TCMR (6%), ABMR (20%) and mixed ABMR/TCMR (1%).
JCI insights 2017 [46] BL (n = 109), TCMR (n = 87) Archetypal analysis of molecular phenotypes.