Validation Study of Gene Expression Signatures Associated with Antibody-Mediated Rejection (ABMR) and Cell-Mediated Rejection (CMR) in Renal Allograft Biopsies (Bx) Suggests Complexity of Molecular Diagnosis for ABMR Compared to CMR

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

¹Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA
²Pathology, Cedars-Sinai Medical Center, Los Angeles, CA
³Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Meeting: 2018 American Transplant Congress

Abstract number: A93

Keywords: Biopsy, Gene expression, Kidney transplantation, Rejection

Session Information

Session Name: Poster Session A: Kidney Acute Antibody Mediated Rejection

Session Type: Poster Session

Date: Saturday, June 2, 2018

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall 4EF

Background: Various molecular signatures specific to ABMR and CMR based on gene expression in renal allograft Bx or peripheral blood mononuclear cells (PBMC) of renal transplant patients have been previously reported. Here we conducted a validation study of previously reported gene expression signatures in patients at our center.

Methods: Total RNA was extracted from 53 Bx (11 ABMR, 14 ABMR+CMR, 15 CMR, 13 no rejection Control) for reverse transcription, pre-amplification and qPCR. 109 rejection-associated candidate genes (32 Bx ABMR, 15 PBMC chronic ABMR, 14 Bx CMR, 16 PBMC acute rejection, 22 PBMC antibody-dependent cellular cytotoxicity and/or memory T cell-specific, and 10 inflammation-related genes) reported in previous studies were examined. The expression levels 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: Among 109 candidate genes, we found significantly different expression levels of 60 genes in Bx when the rejection groups were compared with Controls. However, among 32 genes previously reported to be associated with ABMR in Bx, we only found 3 genes (CCL3, SH2D1B, KLRF1) showing significantly different expression levels when ABMR and ABMR+CMR were compared to CMR and Controls. In contrast, among 14 genes previously reported to be associated with CMR in Bx, we found 10 genes (CTLA4, SIRPG, ANKRD22, BTLA, ICOS, ADAMDEC1, CD72, CD8a, CD28, GBP5) showing significant difference of expression levels when CMR and ABMR+CMR were compared to ABMR and Controls.

Conclusions: In our cohort, genes reported to be associated with CMR showed a significant validation but the validation of ABMR-associated genes was much less significant. This result suggests the complexity of molecular diagnosis for ABMR compared to CMR. This may be due to the various stages of injury at diagnosis (acute vs. chronic ABMR), various molecular mechanisms involved in ABMR, or medication/therapy variations at different centers.

CITATION INFORMATION: Zhang H., Nast C., Doldron J., Cheung M., Vo A., Jordan S., Toyoda M. Validation Study of Gene Expression Signatures Associated with Antibody-Mediated Rejection (ABMR) and Cell-Mediated Rejection (CMR) in Renal Allograft Biopsies (Bx) Suggests Complexity of Molecular Diagnosis for ABMR Compared to CMR Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Zhang H, Nast C, Doldron J, Cheung M, Vo A, Jordan S, Toyoda M. Validation Study of Gene Expression Signatures Associated with Antibody-Mediated Rejection (ABMR) and Cell-Mediated Rejection (CMR) in Renal Allograft Biopsies (Bx) Suggests Complexity of Molecular Diagnosis for ABMR Compared to CMR [abstract]. https://atcmeetingabstracts.com/abstract/validation-study-of-gene-expression-signatures-associated-with-antibody-mediated-rejection-abmr-and-cell-mediated-rejection-cmr-in-renal-allograft-biopsies-bx-suggests-complexity-of-molecular-di/. Accessed November 21, 2024.

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