Assessment of mRNA Gene Profiles in Plasma Exosome to Predict Risk for Antibody-Mediated Rejection (ABMR) of Renal Allografts.

H. Zhang,¹ J. Kahwaji,¹ P. Li,² S. Ge,¹ D. Thomas,¹ C. Nast,³ A. Vo,¹ M. Haas,³ S. Jordan,¹ M. Toyoda.¹

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

Meeting: 2016 American Transplant Congress

Abstract number: D1

Keywords: Gene expression, Kidney transplantation, Prognosis, Rejection

Session Information

Session Name: Poster Session D: Antibody Mediated Rejection: Session #2

Session Type: Poster Session

Date: Tuesday, June 14, 2016

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

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

Location: Halls C&D

Background: ABMR is a major obstacle for successful transplant in HLA-sensitized (HS) patients. Complement-mediated and antibody-dependent cellular cytotoxicity (ADCC) are primarily mechanisms for ABMR. Previously we showed overexpression of ADCC- and IL-6 signaling-related genes in kidney biopsies with ABMR compared to cell-mediated rejection (CMR) and no rejection. mRNA in exosome is known to be well protected in blood. Here we explored a possible utility of exosome mRNA to predict a risk for ABMR.

Methods: Total RNA was extracted from exosome purified from 226 EDTA-plasma of 51 patients (7 ABMR, 6 CMR, 38 no rejection Control [18 HS/20 non-HS]) for reverse transcription, pre-amplification and then qPCR. The results of each gene were presented as fold change (FC) vs. a reference RNA after normalized with a housekeeping gene, GAPDH. The FC was then normalized with the average FC of all samples in the non-HS Control group for each gene (nFC). The average nFC (anFC) of multiple samples of each patient at or prior to diagnosis of rejection and the anFC from the 1st year post-transplant of each patient in the Control group were used for comparison among all groups. A gene score (GS) was calculated by averaging selected 7 genes' anFC for each patient for further comparison.

Results: Among 23 ABMR-associated genes selected from our previous and other published studies, 7 genes (GP130, TNFα, CD160, CCL4, CAV1, DARC, SH2D1B) showed increase of anFC in the ABMR compared to other groups. The GS of these 7 genes was significantly higher in the ABMR than other groups, and also significantly higher in HS Control than CMR and non-HS Control. HS Control patients with relatively higher GS tended to have donor-specific antibodies during the period.

	Gene Score	P Value
	Gene Score	vs. CMR	vs. HS Control	vs. non-HS Control
ABMR	1.77±0.38	0.00	0.01	0.00
CMR	0.71±0.23		0.00	0.12
HS Control	1.28±0.42			0.04
non-HS Control	1.00±0.42

Conclusions: Significant change in ABMR-associated gene expression could be detected in exosome from blood plasma and correlate with ABMR status. This result suggests the possible utility of exosome mRNA measurement to predict a risk for ABMR.

CITATION INFORMATION: Zhang H, Kahwaji J, Li P, Ge S, Thomas D, Nast C, Vo A, Haas M, Jordan S, Toyoda M. Assessment of mRNA Gene Profiles in Plasma Exosome to Predict Risk for Antibody-Mediated Rejection (ABMR) of Renal Allografts. Am J Transplant. 2016;16 (suppl 3).

To cite this abstract in AMA style:

Zhang H, Kahwaji J, Li P, Ge S, Thomas D, Nast C, Vo A, Haas M, Jordan S, Toyoda M. Assessment of mRNA Gene Profiles in Plasma Exosome to Predict Risk for Antibody-Mediated Rejection (ABMR) of Renal Allografts. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/assessment-of-mrna-gene-profiles-in-plasma-exosome-to-predict-risk-for-antibody-mediated-rejection-abmr-of-renal-allografts/. Accessed May 11, 2025.

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