Session Name: Biomarkers, Immune Assessment and Clinical Outcomes
Session Date & Time: None. Available on demand.
*Purpose: Allograft biopsies are considered the gold standard for diagnosis and therapeutic guidance in kidney transplant recipients. Expanding current biopsy assessments to include gene expression signatures may further improve post-transplant monitoring and diagnosis; however, identification and validation of gene subsets for clinical use is required.
*Methods: In this retrospective study, formalin-fixed paraffin embedded kidney allograft tissues from patients with confirmed antibody mediated rejection (ABMR, n=12), T-cell mediated rejection (TCMR, n=8) or BK virus nephropathy (BKVN, n=9) were analyzed using the Nanostring nCounter® platform (Nanostring Technologies, Inc., Seattle, WA). A panel of 758 immune related genes was assessed. Differentially expressed genes were rank-ordered using the Student’s T-test and key genes identified as those with the greatest fold change (FC) and biological significance.
*Results: Patients (n=28) were mostly white men (67%) with a mean age of 51 ± 14 years. Allograft biopsies were primarily for-cause biopsies (80%) performed due to de novo DSA or allograft dysfunction. Preliminary analysis revealed 60 genes differentially expressed between ABMR and BKVN (12 genes), TCMR and BKVN (32 genes) and ABMR and TCMR (16 genes). The strongest up- (FC≥2) or down (FC<0.5) regulated genes of the 60 genes that were identified are shown in Table 1. Upregulated genes helped characterize TCMR vs ABMR (15 genes, mean FC=6.8, range=5.2-13.9), and importantly TCMR vs BKVN (7 genes, mean FC= 2.6, range 2.4-3.7). Notably, AIM2 and BTLA showed upregulation in TCMR compared to both ABMR (FC 5.2 and 6.1, respectively) and BKVN, although the change was more moderate in BK nephropathy (FC 2.5 and 3.4, respectively).
Table 1: Genes with Strongest Differential Expression
|TCMR vs ABMR||TCMR vs BKVN||BKVN vs. ABMR|
|Strongly upregulated (FC ≥ 2.0)||AIM2, SELL, GBP5, LILRB4, ICOS, ANKRD22, FCGR1A, BTLA, C3, CALHM6, CD72, CTLA4, FPR1, LAG3, CCL18||PSTPIP1, CD48, NFAM1, CIITA, TNFSF8, CD86, STAT4||None|
|Strongly downregulated (FC < 0.5)||UMOD||None||HSD11B1, CXCL13|
*Conclusions: Gene expression profiles assessed by Nanostring nCounter® platform may help differentiate ABMR from TCMR, and importantly, TCMR from BKVN. Additional studies are required to validate and confirm these findings
To cite this abstract in AMA style:Degner KR, Swanson KJ, Parajuli S, Mandelbrot D, Garg N, Aziz F, Mohamed M, Zhong W, Ptak L, Wilson NA, Woodward R, Djamali A. Gene Expression Profiles Assessed by the Nanostring nCounter® Platform May Differentiate Different Types of Rejection, and Importantly, T-Cell Mediated Rejection from BK Virus Nephropathy [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/gene-expression-profiles-assessed-by-the-nanostring-ncounter-platform-may-differentiate-different-types-of-rejection-and-importantly-t-cell-mediated-rejection-from-bk-virus-nephropathy/. Accessed June 16, 2021.
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