AlloMap Kidney Gene Expression Profiling Discriminates Rejection from Immuno-Quiescence in Renal Transplant Recipients

E. Akalin¹, A. Djamali², H. Xu³, X. Jin³, R. N. Woodward³, S. Dholakia³, J. S. Bromberg⁴

¹Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, ²University of Wisconsin, Madison, WI, ³CareDx, Brisbane, CA, ⁴University of Maryland School of Medicine, Baltimore, MD

Meeting: 2021 American Transplant Congress

Abstract number: LB 32

Keywords: Gene expression, Kidney transplantation, Rejection

Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes

Session Information

Session Name: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: Assessment of immune activation is important when considering pathologies such as allograft rejection as well as potential interventions that may extend allograft survival. Optimizing interventions by assessing impact through quantifiable measures such as biomarker changes can drive the paradigm shift from reactive to proactive care. Here we describe validation of a blood gene expression profile (GEP) to inform on both T cell-mediated (TCMR) and antibody-mediated (ABMR) rejection.

*Methods: A classifier using 5 informative genes was developed to discriminate quiescence from rejection using 21 samples from healthy, stable patients (HS, no clinical signs or symptoms) and 18 active rejection samples from the DART study (NCT02424227) patients. The “AlloMap Kidney” GEP signature was validated in an independent set of samples from the DART study using the targeted RNA sequencing. The validation samples comprised 45 non-rejection (NR, negative for-cause biopsy); 28 quiescent (Q, negative protocol biopsy); 27 HS; 7 T cell-mediated rejection (TCMR), 10 antibody-mediated rejection (ABMR), and 1 mixed rejection. In addition to AlloMap Kidney GEP, AlloSure dd-cfDNA was also performed.

*Results: AlloMap Kidney scores (range 0-20) were significantly different between the control groups (Q, NR, HS) and rejection groups (ABMR, TCMR, Combined Rejections) (Figure). Median (IQR) results: Q=8.77 (7.52-11.11), NR=10.12 (8.15-12.17), HS=9.45 (8.26-11.55), ABMR = 11.50 (10.84-13.15), TCMR=15.14 (12.93-16.69). The scores of the combined rejection group were statistically significant from that of both the NR (p=0.003) and Q groups (p=0.001); and the ROC analysis demonstrated an AUC of 0.77 (95% CI 0.70-0.84) and 0.81 (95% CI 0.74-0.88), respectively. Sub-study assessment of the TCMR results showed that higher grade rejection samples have generally higher AlloMap scores.

*Conclusions: Validation of AlloMap Kidney GEP provides a strong indication of the ability to distinguish graft rejection from immune quiescence. Quantification across a range of scores allows dynamic assessment compared to binary outputs and supports the applicability observed in heart transplantation. AlloMap Kidney has a strong association with TCMR and also identifies AMR. The performance suggests a complementary use with AlloSure for dd-cfDNA, combining immunological assessment with informative data on allograft injury.

To cite this abstract in AMA style:

Akalin E, Djamali A, Xu H, Jin X, Woodward RN, Dholakia S, Bromberg JS. AlloMap Kidney Gene Expression Profiling Discriminates Rejection from Immuno-Quiescence in Renal Transplant Recipients [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/allomap-kidney-gene-expression-profiling-discriminates-rejection-from-immuno-quiescence-in-renal-transplant-recipients/. Accessed November 24, 2024.

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