Similar Elevation of Gene Expression Associated with Antibody-Mediated Rejection (ABMR) of Renal Allografts Can Be Detected in Both Plasma Exosomes (pExo) and Biopsies (Bx) by Assessing mRNA Transcript Profiles.
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: 399
Keywords: Gene expression, Kidney transplantation, Rejection, Reverse transcriptase PCR
Session Information
Session Name: Concurrent Session: Diagnosis of Antibody Mediated Rejection in Kidney Transplant Recipients
Session Type: Concurrent Session
Date: Tuesday, May 2, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
Location: E354a
Background: ABMR is a major obstacle for successful transplant in HLA-sensitized patients (Pts). Prediction of ABMR by non-invasive diagnostic tools is desirable. Previously we showed overexpression of ABMR-associated genes in Pts with ABMR compared to cell-mediated rejection (CMR) and (&) no rejection using either kidney Bx or pExo. Here we studied the correlation of mRNA transcript profiles between Bx & pExo from same Pts with or without ABMR.
Methods: Total RNA was extracted from both 26 Bx & 40 pExo samples purified from EDTA-plasma collected within 1 month prior to each Bx in 26 Pts (10 ABMR, 8 CMR, 8 no rejection Control), then submitted for reverse transcription, pre-amplification and qPCR on 25 ABMR- &/or inflammation-associated genes. The results were presented as relative quantity (RQ) vs. a reference RNA after normalized by housekeeping GAPDH gene. The average RQ of multiple pExo RNA samples of same Pt for each gene were used for further comparisons among all groups.
Results: Among the 25 genes tested, mRNA transcript level of SH2D1B (a NK cell specific gene) consistently showed significant elevation in ABMR above CMR & Control for both pExo & Bx samples. Similar elevation was detected for chemokine CCL3 in ABMR & CMR above Control for both pExo & Bx (Table 1). IFNγ, CD160, CRTAM & CCL4 mRNA transcript levels were elevated in both ABMR &/or CMR as detected for Bx, but not for pExo.
| Genes | RQ | ||
| ABMR | CMR | Control | |
| SH2D1B (Bx) | 7.8±6.2*,** | 1.7±2.0 | 1.5±1.2 |
| SH2D1B (pExo) | 39±22#,** | 11±6 | 22±15 |
| CCL3 (Bx) | 0.06±0.05* | 0.03±0.03* | 0.00±0.00 |
| CCL3 (pExo) | 0.02±0.02* | 0.01±0.01# | 0.00±0.00 |
*p<0.05 & #0.05<p<0.1 vs. Control; **p<0.05 vs. CMR
Conclusions: Similar elevated mRNA transcript levels for certain rejection-associated genes including SH2D1B & CCL3 can be detected in both Bx & pExo, and correlated with rejection status. These results suggest the possible utility of pExo mRNA measurement to predict a risk for ABMR &/or CMR, as a non-invasive diagnostic tool that may complement traditional biopsy assessments.
CITATION INFORMATION: Zhang H, Nast C, Doldron J, Cheung M, Mirocha J, Kahwaji J, Vo A, Jordan S, Toyoda M. Similar Elevation of Gene Expression Associated with Antibody-Mediated Rejection (ABMR) of Renal Allografts Can Be Detected in Both Plasma Exosomes (pExo) and Biopsies (Bx) by Assessing mRNA Transcript Profiles. 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. Similar Elevation of Gene Expression Associated with Antibody-Mediated Rejection (ABMR) of Renal Allografts Can Be Detected in Both Plasma Exosomes (pExo) and Biopsies (Bx) by Assessing mRNA Transcript Profiles. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/similar-elevation-of-gene-expression-associated-with-antibody-mediated-rejection-abmr-of-renal-allografts-can-be-detected-in-both-plasma-exosomes-pexo-and-biopsies-bx-by-assessing-mrna-transcrip/. Accessed November 22, 2024.« Back to 2017 American Transplant Congress