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Molecular Testing for Microcirculation Injury Enhances the Assessment of Antibody-Mediated Rejection in Human Cardiac Allograft Biopsies

B. Afzali,1 E. Chapman,1 B. Adam,1 F. Riesgo Gil,2 D. Kim,2 L. Hidalgo,1 P. Campbell,1 B. Sis,1 M. Mengel.1

1Dept. of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
2Div. of Cardiology, University of Alberta, Edmonton, AB, Canada.

Meeting: 2015 American Transplant Congress

Abstract number: B273

Keywords: Antibodies, Graft survival, Heart transplant patients, Rejection

Session Information

Session Name: Poster Session B: Translational Genetics and Proteomics in Transplantation

Session Type: Poster Session

Date: Sunday, May 3, 2015

Session Time: 5:30pm-6:30pm

 Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

BACKGROUND: Despite continuous attempts to refine diagnostic consensus, accurate assessment of Antibody-mediated rejection (AMR) is an ongoing unmet need. The microcirculation represents the primary target for donor-specific, anti HLA antibodies (DSA), accordingly increased expression of endothelial, NK cell and inflammatory genes has been associated with AMR. Here we evaluate a respective gene set for diagnosing AMR in formalin-fixed, paraffin-embedded (FFPE) human cardiac graft biopsies.

METHODS: 107 archival FFPE biopsies were classified according to 2013 ISHLT consensus. A set of 34 endothelial, NK cell and inflammatory genes was quantified with NanoString nCounter system.

RESULTS: In 70 AMR cases gene set expression was significantly higher compared to 22 ACR (p<0.0001) and 15 control cases (p<0.0001). Overall presence of DSA was associated with higher gene set expression (p=0.001). In the presence of DSA AMR cases tended to higher gene expression but this did not meet statistical significance (p=0.065), whereas in ACR presence of DSA did not result in higher expression (Figure 1A). C4d deposition showed borderline association with higher expression levels (p=0.052). Significant higher expression were found between pAMR2 and pAMR1H+ compared to ACR and controls. In ROC analysis the gene set had higher diagnostic accuracy (AUC=78.61) for discriminating AMR from ACR and controls than DSA (AUC=72.55) or C4d (AUC=70.71). In 17 patients with sequential biopsies increasing gene set expression over the course of AMR was associated with allograft failure (Figure 1B).

CONCLUSION: Molecular diagnostics in FFPE allograft biopsies is feasible as routine diagnostic work-up. Molecular grading of antibody-mediated tissue injury can add diagnostic and prognostic value to assessing cardiac allograft biopsies.

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To cite this abstract in AMA style:

Afzali B, Chapman E, Adam B, Gil FRiesgo, Kim D, Hidalgo L, Campbell P, Sis B, Mengel M. Molecular Testing for Microcirculation Injury Enhances the Assessment of Antibody-Mediated Rejection in Human Cardiac Allograft Biopsies [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/molecular-testing-for-microcirculation-injury-enhances-the-assessment-of-antibody-mediated-rejection-in-human-cardiac-allograft-biopsies/. Accessed May 9, 2025.

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