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Abstract: PO2556

Molecular Analysis of Renal Graft Biopsies: Comparing the Edmonton Molecular Microscope with the NanoString Human Organ Transplant Panel

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Schmitz, Jessica, Hannover Medical School, Medizinische Hochschule Hannover, Institute of Pathology, Nephropathology Unit, Hannover, Niedersachsen, Germany
  • Stark, Helge, Hannover Medical School, Institute of Pathology, Hannover, Germany
  • Bartels, Stephan, Hannover Medical School, Institute of Pathology, Molecular Pathology, Hannover, Germany
  • Jonigk, Danny, Hannover Medical School, Institute of Pathology, Hannover, Germany
  • Halloran, Philip F., University of Alberta, Edmonton, Edmonton, Alberta, Canada
  • Einecke, Gunilla, Hannover Medical School, Department of Nephrology and Hypertension, Hannover, Germany
  • Braesen, Jan H., Hannover Medical School, Medizinische Hochschule Hannover, Institute of Pathology, Nephropathology Unit, Hannover, Niedersachsen, Germany
Background

The renal transplant biopsy is the diagnostic gold standard and usually evaluated with the continuously expanded and updated Banff classification which is based on on descriptive, empirically-derived criteria and thus lacks precision. High-resolution determination of the graft inflammation by NanoString analysis, which was developed for formalin-fixed paraffin-embedded-derived (FFPE) RNA, should be a sufficient approach for objective molecular diagnosis of renal transplant biopsies and may improve our understanding of graft biology.

Methods

We used well-annotated surveillance and indication biopsies from 63 patients whose time-matched second biopsy core had been frozen and analyzed by microarray in the INTERCOM/INTERCOMEX study. After reevaluation according to recent Banff consensus, RNA isolation of the FFPE biopsy was performed and led to sufficient RNA yields in 53 samples which were further processed for NanoString analysis using the nCounter Human Organ Transplant Panel.

Results

Morphologically, of the 53 samples analyzed (samples from 2011/12 and 2015), twenty-five patients showed no signs of rejection, twelve had borderline rejection, four showed cellular rejection, seven had humoral rejection, and five presented with combined rejection. Preliminary analysis of gene expression by T-distributed Stochastic Neighbor Embedding (t- SNE), Random Forest and Principal Component Analysis (PCA) showed clear differences between samples with rejection (humoral and cellular) and without rejection. Rejection samples revealed high expression of chemokine ligands compared to rejection-free tissues. A common pattern of samples without rejection and borderline rejection was observed. Our results displayed good correlation with the former molecular microarray-based diagnosis from the INTERCOM/INTERCOMEX study.

Conclusion

Molecular diagnostic approach using the NanoString platform may supplement morphological diagnosis of renal grafts especially in unclear cases and thus enhance precision diagnostics with small tissue requirement. Morphological and molecular evaluation in the same biopsy core from FFPE tissue enables direct histological-molecular correlation. Additionally, this technology also improves our understanding of pathophysiology in renal and other transplants.