Date: Tuesday, May 2, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
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.
*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 June 20, 2021.
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