Gene Expression Signatures Associated with Antibody-Mediated Rejection (ABMR) in Renal Allograft Biopsies (Bx) Are Beneficial to Clarifying ABMR Activity in Ambivalent Cases
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: 248
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: 4:15pm-4:27pm
Location: Virtual
*Purpose: “Thoroughly validated gene transcripts” in renal Bx was adopted as one of the criteria for ABMR diagnosis in the latest Banff classification. Here, we assessed possible ABMR activity in Bx whose pathology findings did not meet the current Banff criteria for either active or chronic active ABMR, using gene expression signatures associated with ABMR, identified in Bx with definitive pathology diagnosis.
*Methods: Total RNA was extracted from Bx for reverse transcription, pre-amplification and qPCR to measure mRNA transcript levels of various genes. 4 genes (KLRF1, SH2D1B, CCL3, CCL4) with the most significant association with ABMR were identified from 66 Bx (30 ABMR, 15 T-cell-mediated rejection [CMR], 10 ABMR+CMR, and 11 no rejection controls) excluding chronic ABMR, suspicious ABMR or borderline CMR cases. ABMR gene score (GS) was calculated based on the mRNA transcript levels of these 4 genes. The ABMR GS was evaluated for 16 Bx which were suspicious for ABMR but did not meet the current Banff criteria for any type of ABMR (Table 1), and also for 12 Bx meeting the current Banff criteria of chronic ABMR but not chronic active ABMR.
*Results: Based on the discovery set of 66 Bx, an ABMR GS of 0.43 and above was set for the diagnosis of active ABMR (AUC: 0.897, sensitivity: 0.850, specificity: 0.846). Of the 16 Bx suspicious for ABMR, 15 (94%) had ABMR GS above 0.43 (1.20±0.54) and 1 was 0.39. Of the 15 Bx with ABMR GS above 0.43, 6 (40%) had additional Bx-proven active or chronic active ABMR within 1 year before or after each Bx. Of the 12 chronic ABMR Bx, 6 (50%) had ABMR GS above 0.43 (1.47±0.55), and 6 were below 0.43 (0.20±0.09); microvascular inflammation (MVI: g+ptc) was not different between these two subgroups (p=0.88).
| # of Bx | g+ptc | g | C4d+ | DSA+ | (Borderline) CMR | Others | ABMR GS |
| 10 | ≥3 | ≥1 | No | No | Various | N/A | >0.43 |
| 1 | 3 | 1 | No | No | Yes | N/A | 0.39 |
| 1 | 2 | 0 | Yes | Yes | Yes | N/A | >0.43 |
| 2 | ≥2 | 0 | No | Various | No | N/A | >0.43 |
| 2 | 2 | 0 | No | No | Yes | Both Bx were from the same patient who had pre-existing DSA that was detected again along with Bx-proven active ABMR within 1 year after these 2 Bx. | >0.43 |
*Conclusions: Our ABMR GS confirmed ABMR activity in 15 out of 16 Bx suspicious for active or chronic active ABMR. 50% of 12 chronic ABMR Bx had ABMR GS above 0.43, suggesting an active ABMR component despite the lack of pathological diagnostic features for ABMR activity. Our ABMR GS exhibited significant utility for identifying ABMR activity in renal allograft Bx with diagnostically ambivalent pathological features and may be a valuable tool in guiding therapeutic decisions.
To cite this abstract in AMA style:
Zhang H, Nast CC, Ammerman N, Vo AA, Gallegos I, Arevalo M, Jordan SC, Toyoda M. Gene Expression Signatures Associated with Antibody-Mediated Rejection (ABMR) in Renal Allograft Biopsies (Bx) Are Beneficial to Clarifying ABMR Activity in Ambivalent Cases [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/gene-expression-signatures-associated-with-antibody-mediated-rejection-abmr-in-renal-allograft-biopsies-bx-are-beneficial-to-clarifying-abmr-activity-in-ambivalent-cases/. Accessed November 22, 2024.« Back to 2020 American Transplant Congress