Donor Derived Cell Free DNA (dd-cfDNA) and Gene Expression Signatures of Antibody-Mediated Rejection (ABMR) May Improve Accuracy of ABMR Diagnosis (Dx)
1Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, 2Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 3Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
Meeting: 2020 American Transplant Congress
Abstract number: 246
Keywords: Biopsy, Gene expression, Kidney transplantation, Rejection
Session Information
Session Name: Kidney Chronic Antibody Mediated Rejection
Session Type: Oral Abstract Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:45pm
Presentation Time: 3:51pm-4:03pm
Location: Virtual
*Purpose: Dd-cfDNA has a clinically meaningful association with early Dx of ABMR. Here, we evaluated dd-cfDNA measured prior to for-cause biopsies (Bx), and also measured gene transcripts associated with ABMR in these Bx, to determine if combined utility could improve diagnostic accuracy.
*Methods: 61 Bx from 55 patients with dd-cfDNA tests done within 1 month (0.5±0.3 M) prior to each Bx were submitted for gene expression analysis to obtain the ABMR gene scores (GS). The diagnostic criterion for ABMR with GS calculated from mRNA transcript levels of 4 genes (KLRF1, SH2D1B, CCL3, CCL4) was ≥0.43 based on a previous discovery set of Bx with definitive pathology Dx. Overall correlation analysis of dd-cfDNA (≥1% for Dx of any rejection) and ABMR GS with pathology was made.
*Results: Although Dx by dd-cfDNA did not confirm T-cell-mediated rejection (CMR) in the majority of Bx with CMR alone (dd-cfDNA confirmed rejection in 4/9 Bx [44%], 5.3±3.5), ABMR as seen in 20 Bx with pathology Dx of active ABMR (A-ABMR) or chronic active ABMR (C/A-ABMR) was confirmed by both dd-cfDNA (19 Bx [95%], 2.5±1.8) and ABMR GS (17 Bx [85%], 1.39±1.60) with a significant success. Of 3 Bx which were A-ABMR or C/A-ABMR by pathology Dx with dd-cfDNA all >1% but ABMR GS all <0.43, 1 Bx with GS at 0.39 was obtained after plasma-exchange and another (GS: 0.07) was also after anti-ABMR treatment with pathology showing very mild A-ABMR, suggesting ABMR GS being more sensitive to anti-ABMR treatment than dd-cfDNA. For 13 Bx with pathology Dx of chronic but not active ABMR (C-ABMR) or suspicious for A-ABMR or C/A-ABMR, ABMR GS confirmed ABMR activity with higher precision (85%) than dd-cfDNA (62%), with 6 Bx (46%) in common. Finally, 2 Bx with pure CMR and 1 with no rejection showed ABMR GS >0.43 and dd-cfDNA >1%, suggesting possible early ABMR activity.
| Pathology Dx | # of Bx | # of Bx with dd-cfDNA≥1% (dd-cfDNA) | # of Bx with ABMR GS≥0.43 (ABMR GS) | # of Bx with dd-cfDNA≥1% & ABMR GS≥0.43 (dd-cfDNA/ABMR GS) |
| A-ABMR & C/A-ABMR | 20 | 19 (2.5±1.8) | 17 (1.39±1.60) | 16 (2.4±1.8/1.42±1.65) |
| C-ABMR & Suspicious for A-ABMR or C/A-ABMR | 13 | 8 (2.5±2.2) | 11 (1.08±0.43) | 6 (2.7±2.6/1.13±0.38) |
| CMR | 9 | 4 (5.3±3.5) | 3 (0.46±0.03) | 2 (5.6±3.1/0.45±0.04) |
| Borderline CMR | 4 | 0 | 0 | 0 |
| No Rejection | 15 | 2 (3.2±2.9) | 3 (1.02±0.59) | 1 (5.2/0.88) |
*Conclusions: Both dd-cfDNA and ABMR GS perform well in ABMR diagnosis. ABMR GS appears to clarify ABMR activity where ambivalent pathologic features of ABMR are seen. Additionally, ABMR GS has the potential of predicting patients’ responses to anti-ABMR treatment. Combining ABMR GS and dd-cfDNA appears to detect ABMR-specific immune activation when Bx show no rejection or features of CMR alone.
To cite this abstract in AMA style:
Zhang H, Nast CC, Huang E, Ammerman N, Vo AA, Jordan SC, Toyoda M. Donor Derived Cell Free DNA (dd-cfDNA) and Gene Expression Signatures of Antibody-Mediated Rejection (ABMR) May Improve Accuracy of ABMR Diagnosis (Dx) [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-dd-cfdna-and-gene-expression-signatures-of-antibody-mediated-rejection-abmr-may-improve-accuracy-of-abmr-diagnosis-dx/. Accessed November 22, 2024.« Back to 2020 American Transplant Congress