Intragraft Gene Expression Differentiates Polyomavirus Nephropathy from T-Cell Mediated Rejection

B. Adam,¹ S. Wagner,¹ J. Bräsen,² V. Bröcker,² V. D'Agati,³ C. Drachenberg,⁴ E. Farkash,⁵ A. Farris,⁶ L. Geldenhuys,⁷ A. Magil,⁸ V. Nickeleit,⁹ P. Randhawa,¹⁰ H. Regele,¹¹ M. Mengel.¹

¹University of Alberta, Edmonton, Canada
²Hannover Medical School, Hannover, Germany
³Columbia University, New York
⁴University of Maryland, College Park
⁵University of Michigan, Ann Arbor
⁶Emory University, Atlanta
⁷Dalhousie University, Halifax, Canada
⁸University of British Columbia, Vancouver, Canada
⁹University of North Carolina, Chapel Hill
¹⁰University of Pittsburgh, Pittsburgh
¹¹Medical University of Vienna, Vienna, Austria.

Meeting: 2018 American Transplant Congress

Abstract number: 461

Keywords: Gene expression, Kidney transplantation, Polyma virus, Rejection

Session Information

Session Name: Concurrent Session: Kidney: Polyoma

Session Type: Concurrent Session

Date: Tuesday, June 5, 2018

Session Time: 2:30pm-4:00pm

Presentation Time: 2:54pm-3:06pm

Location: Room 2AB

Background: Improved immunosuppression protocols have reduced the incidence of T-cell mediated rejection (TCMR) but still carry a significant risk of BK polyomavirus nephropathy (BKVN). Despite requiring opposite treatments, BKVN and TCMR often have overlapping clinical and histological presentations. Molecular testing may allow for more precise assessment.

Methods: NanoString was used to measure the expression of 800 genes in 40 formalin-fixed paraffin-embedded human samples. The genes included 795 human immune-related genes and 5 polyomavirus (PV) genes (Agnoprotein, LTAg, VP1, VP2, VP3). The samples included native kidney BKVN (n=5), pure TCMR (n=9), SV40-positive carcinoma (tumor BK, n=9), and normal implant kidney biopsies (n=8). Using six additional nephrectomies with mixed BKVN and TCMR, regions showing histological features of only BKVN (mixed BKVN, n=6) and only TCMR (mixed TCMR, n=3) were isolated with laser capture microdissection. Differential gene expression and diagnostic performance were assessed.

Results: All five PV genes were significantly increased (FDR<0.05) in native BKVN versus pure TMCR but no human genes were differentially expressed. PV gene expression was also significantly higher (versus pure TCMR) in tumor BK (p<0.01), mixed BKVN (p<0.001), and mixed TCMR (p<0.05, except VP1). ROC analysis revealed excellent discrimination between BK-positive (including mixed TCMR) and BK-negative cases (AUC=0.96-1.00). As a 5-gene set, the PV genes demonstrated near-perfect diagnostic performance (AUC=0.99) with improved sensitivity (0.96) over histology (0.87).

Conclusion: These data suggest that PV gene expression is more sensitive than histology and can more precisely discriminate BKVN and TCMR. However, at the molecular level, no significant difference in immune response was identified.

CITATION INFORMATION: Adam B., Wagner S., Bräsen J., Bröcker V., D'Agati V., Drachenberg C., Farkash E., Farris A., Geldenhuys L., Magil A., Nickeleit V., Randhawa P., Regele H., Mengel M. Intragraft Gene Expression Differentiates Polyomavirus Nephropathy from T-Cell Mediated Rejection Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Adam B, Wagner S, Bräsen J, Bröcker V, D'Agati V, Drachenberg C, Farkash E, Farris A, Geldenhuys L, Magil A, Nickeleit V, Randhawa P, Regele H, Mengel M. Intragraft Gene Expression Differentiates Polyomavirus Nephropathy from T-Cell Mediated Rejection [abstract]. https://atcmeetingabstracts.com/abstract/intragraft-gene-expression-differentiates-polyomavirus-nephropathy-from-t-cell-mediated-rejection/. Accessed November 21, 2024.

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