Biopsies (Bx) of Renal Allografts with Antibody- + Cell-Mediated Rejection (ABMR/CMR) Exhibit Gene Expression Signatures from Both Types of Rejection.

H. Zhang,¹ C. Nast,² J. Doldron,² M. Cheung,² J. Mirocha,³ J. Kahwaji,¹ A. Vo,¹ S. Jordan,¹ M. Toyoda.¹

¹Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles
²Pathology, Cedars-Sinai Medical Center, Los Angeles
³Biostatistics Center, Cedars-Sinai Medical Center, Los Angeles

Meeting: 2017 American Transplant Congress

Abstract number: B82

Keywords: Biopsy, Kidney transplantation, Rejection, Reverse transcriptase PCR

Session Information

Session Name: Poster Session B: Antibody Mediated Rejection in Kidney Transplant Recipients II

Session Type: Poster Session

Date: Sunday, April 30, 2017

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Background: In HLA-sensitized kidney transplant patients (Pts) the concomitant presence of ABMR/CMR on Bx is associated with a more severe and (&) usually irreversible injury profile compared to either ABMR or CMR alone. Previously, we showed overexpression of antibody-dependent cell-mediated cytotoxicity- & other inflammation-associated genes in Bx of ABMR Pts compared to CMR and no rejection Control. Here we investigated the mRNA transcript profiles for a similar group of genes in Bx from Pts with/without ABMR, CMR or combined ABMR/CMR.

Methods: Total RNA was extracted from 54 Bx (12 ABMR, 10 combined ABMR/CMR, 19 CMR, 13 no rejection Control) for reverse transcription, pre-amplification and qPCR on 25 possibly rejection-associated genes. The results of each gene were presented as relative quantity (RQ) vs. a reference RNA after normalized by housekeeping GAPDH gene. Comparisons were made among 4 groups.

Results: Comparing ABMR, CMR & Control, the mRNA transcript levels of 14 tested genes were significantly elevated in ABMR &/or CMR above Control (results of 6 representative genes shown in Table below). Meanwhile any gene with significant elevation in either ABMR or CMR was also significantly elevated in Pts with combined ABMR/CMR.

Genes	RQ
Genes	ABMR/CMR	ABMR	CMR	Control
CCL3	0.07±0.07^*,[spades]	0.05±0.05^{*,[spades][spades]}	0.03±0.03^*	0.01±0.02
SH2D1B	7.5±8.5^*,[spades]	6.5±6.4^{*,[spades][spades]}	1.8±1.9	1.0±1.2
IL-10	7.2±7.6^*,#	1.5±2.3	6.9±7.1^*,#	1.1±1.7
IL-21	0.05±0.08^*,##	0.01±0.03	0.20±0.44^*,#	0.002±0.006
IFNγ	0.23±0.28^*,#	0.04±0.04^*	0.10±0.14^*	0.005±0.007
TNFα	0.18±0.14^*	0.15±0.14^*	0.15±0.17^*	0.05±0.05

*p<0.05 & **0.05≤p<0.1 vs. Control; #p<0.05 & ##0.05≤p<0.1 vs. ABMR; [spades]p<0.05 & [spades][spades]0.05≤p<0.1 vs. CMR

Conclusions: Bx from Pts with combined ABMR/CMR exhibited elevation of gene expression from both ABMR & CMR, suggesting that the immune activations specific to either ABMR or CMR are likely activated simultaneously in combined ABMR/CMR, resulting in a more severe and irreversible injury profile.

CITATION INFORMATION: Zhang H, Nast C, Doldron J, Cheung M, Mirocha J, Kahwaji J, Vo A, Jordan S, Toyoda M. Biopsies (Bx) of Renal Allografts with Antibody- + Cell-Mediated Rejection (ABMR/CMR) Exhibit Gene Expression Signatures from Both Types of Rejection. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Zhang H, Nast C, Doldron J, Cheung M, Mirocha J, Kahwaji J, Vo A, Jordan S, Toyoda M. Biopsies (Bx) of Renal Allografts with Antibody- + Cell-Mediated Rejection (ABMR/CMR) Exhibit Gene Expression Signatures from Both Types of Rejection. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/biopsies-bx-of-renal-allografts-with-antibody-cell-mediated-rejection-abmrcmr-exhibit-gene-expression-signatures-from-both-types-of-rejection/. Accessed November 21, 2024.

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