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Abstract: PO2389

Immunohistochemical and Molecular Characterization of Immune Cells in Pediatric Renal Allografts: Mononuclear Phagocytes Correlate with Rejection, Re-Transplantation, Graft Function, and Fibrosis

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Schmitz, Jessica, Hannover Medical School, Institute of Pathology, Nephropathology Unit, Hannover, Germany
  • Senger, Sarah, Hannover Medical School, Institute of Pathology, Nephropathology Unit, Hannover, Germany
  • Khalifa, Abedalrazag Ahmad, Hannover Medical School, Institute of Pathology, Nephropathology Unit, Hannover, Germany
  • Stark, Helge, Hannover Medical School, Institute of Pathology, Hannover, Germany
  • Jonigk, Danny, Hannover Medical School, Institute of Pathology, Hannover, Germany
  • Pape, Lars, Hannover Medical School, Pediatric Nephrology, Hannover, Germany
  • Braesen, Jan H., Hannover Medical School, Institute of Pathology, Nephropathology Unit, Hannover, Germany
Background

Standardized markers of immune cell infiltration may improve diagnostics in renal grafts. To date, no larger study investigating the role of immune cells in renal pediatric allografts exists and their impact on long-term outcome is poorly understood. Children are more prone to graft tolerance, have a more naive immune system and adaptive immune responses to allografts thus might differ from adults.

Methods

Renal graft samples (n=202) from 59 pediatric patients (63% male, mean age 10 years) transplanted 2000-2017 at our center were re-evaluated according to recent Banff criteria and stained for macrophages, dendritic cells, B cells and T cells (CD68, CD206, CD163L1, CD209, CD20, CD3). Quantification of immune cells was performed in whole slide images (WSI) using image analysis software (QuPath). Results were obtained separately for cortex, medulla and extrarenal tissue and displayed as percentages (%) of positively stained area. Additionally, RNA was isolated from paraffin tissue and used for quantification of >700 gene transcripts related to graft immunology (NanoString Human Organ Transplant Panel).

Results

In TCMR (T cell-mediated) and ABMR (antibody-mediated) rejection cortical macrophages were more frequent than in samples without rejection. B cells were most abundant in TCMR. In re-transplants a higher density of macrophages than in first allografts was observed. Protocol biopsies had lower macrophage numbers than indication biopsies. Infiltration of dendritic cells revealed higher densities in samples with i-IFTA. Macrophage numbers correlated negatively with kidney function (eGFR) and positively with fibrosis. Results obtained by NanoString technology confirmed high expression of macrophage-associated gene trancripts (e.g. CCL2, CXCL10) during graft rejection and stratified samples according to Banff morphological diagnosis.

Conclusion

Infiltrating immune cells, particularly mononuclear phagocytes, are highly abundant in pediatric renal transplants in rejection, re-transplantation and fibrosis and might influence long-term graft function. Gene expression analysis using the NanoString Human Organ Transplant Panel may supplement and confirm morphological diagnosis.