Title: Intragraft Gene Expression of Polyomavirus Associated Nephropathy
Authors: Naesens, Maarten ×
Sigdel, T
Salomonis, N
Roedder, S
Gao, X
Vitalone, M
Kuypers, Dirk
Lerut, Evelyne
Sarwal, M #
Issue Date: 2013
Publisher: Munksgaard International Publishers
Host Document: American Journal of Transplantation vol:13 issue:S5 pages:95-95
Conference: 13th American Transplant Congress (ATC) location:Seattle: WA date:MAY 18-22, 2013
Although the histopathology of polyomavirus nephropathy (PVAN) is very often indistinguishable from T-cell mediated rejection (TCMR), the outcome of both diseases is very different. The underlying pathophysiology is however unclear.
Global gene expression was evaluated in 60 post-transplant renal allograft biopsies using Affymetrix HG U133 plus 2.0 microarrays: 15 biopsies with PVAN, 15 with TCMR, and 30 matched control (NL) samples. Data analysis and pathway enrichment analysis was performed using GO-Elite, AltAnalyze and LineageProfiler. In addition, immunohistochemistry for SV40, CD3, CD4, CD8, CD20, CD27, CD68, CD79, FOXP3, MUM1, NCAM, TIA1 and HLA-DR was performed on independent samples (19 TCMR, 19 PVAN).
There was a clear difference in intragraft gene expression between PVAN vs. NL (6472 probesets), and between TCMR vs. NL samples (2483 probesets). In the analysis comparing TCMR vs. NL, and PVAN vs. NL, there was substantial overlap between these probeset lists (958 probesets). Pathway enrichment analysis showed significant overrepresentation of immune gene expression in both PVAN and TCMR, along with specific computationally inferred human immune cell markers (monocyte and memory T-cell). These data were confirmed by RT-PCR. Unique to PVAN samples however, there was an overrepresentation of plasma-cell specific genes, and also mitochondrial gene expression was significantly enriched in PVAN vs. NL/TCMR. The clear overlap between PVAN and TCMR in gene expression signature was confirmed by routine histology in an independent patient cohort, where routine histology did not differentiate PVAN from TCMR. No differences were noted between both diseases for all above cell-specific stains, except for a significantly higher presence of plasma cells and B cells in PVAN compared to TCMR, which confirmed the microarray gene expression data.
PVAN and TCMR have a very similar profile of graft infiltrating cells, except for a significant difference in plasma cell infiltrates both in gene expression analysis and by immunohistochemical studies in PVAN compared to TCMR. Overrepresentation of plasma cells in PVAN could partly explain the worse prognosis of polyomavirus-associated tubulo-interstitial inflammation compared to TCMR-associated tubulo-interstitial inflammation. Further validation of the other significant pathways in this analysis is underway.
ISSN: 1600-6135
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory of Nephrology
× corresponding author
# (joint) last author

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