Validation of Gene Expression Signatures Associated with Antibody-Mediated Rejection (ABMR) in Renal Allograft Biopsies (Bx) of HLA-Sensitized Patients
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: 2019 American Transplant Congress
Abstract number: A187
Keywords: Biopsy, Gene expression, Highly-sensitized, Rejection
Session Information
Session Name: Poster Session A: Kidney Chronic Antibody Mediated Rejection
Session Type: Poster Session
Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: “Thoroughly validated gene transcripts” in renal Bx was adopted as one of the criteria for ABMR diagnosis in the latest Banff classification. Previously, we identified a combination of 3 genes associated with ABMR. Here, we measured the mRNA transcript levels of these genes in Bx samples from 21 HLA-sensitized patients to further validate the assay for better ABMR diagnosis.
*Methods: Total RNA was extracted from 39 Bx (19 ABMR, 4 highly suspicious ABMR, 16 non-ABMR [9 cell-mediated rejection, 7 no rejection]) for reverse transcription, pre-amplification and qPCR to measure mRNA transcript levels of 3 genes (KLRF1, SH2D1B, CCL3). The mRNA levels were expressed as relative quantity vs. a reference RNA after normalized by GAPDH gene, and then ABMR gene scores (GS) were calculated. The GS diagnostic criterion for ABMR was ≥ 0.68.
*Results: Of 39 Bx, 25 (14 ABMR [Table-G1], 11 Non-ABMR [G4]) showed consistent results as assessed by pathology diagnosis and GS. Pathology in 4 Bx (Suspicious ABMR [G2]) was confirmed by GS, while others (G3 and G5) showed inconsistent results by pathology and GS. The GS in 5 ABMR Bx (G3) were < 0.68; 2 were from the same ABOi transplant patient, 1 was a chronic but not active ABMR Bx with low microvascular inflammation (MVI, g+ptc:1), and 1 (GS: 0.62) was a Bx post-Clazakizumab (CLZ) treatment with significant decrease of MVI and disappearance of donor-specific antibody (DSA) vs. pre-CLZ Bx (GS: 2.56), suggesting improvement of ABMR status. The GS in 5 Non-ABMR Bx (G5) were > 0.68; 2 would be ABMR if confirmed by “thoroughly validated gene transcripts” based on their pathology and the latest Banff criteria, and the other 3 Bx all had significant MVI (g+ptc: 2-3) from a patient with DSA history, thus their MVI may be caused by ABMR.
| Bx Diagnosis | Case # (%) | GS | Consistent with GS | g+ptc |
| G1. ABMR | 14 (35.9) | 3.48 ± 3.70 | Yes | 3.6 ± 1.5 |
| G2. Suspicious ABMR | 4 (10.3) | 1.33 ± 0.48 | Yes | 3.3 ± 1.0 |
| G3. ABMR | 5 (12.8) | 0.44 ± 0.22 | No | 2.8 ± 1.1 |
| G4. Non-ABMR | 11 (28.2) | 0.22 ± 0.18 | Yes | 0.5 ± 0.8 |
| G5. Non-ABMR | 5 (12.8) | 1.57 ± 0.82 | No | 3.0 ± 1.0 |
*Conclusions: 64% of the 39 tested Bx showed consistent diagnosis by pathology and GS, while GS confirmed suspicious pathology-based ABMR for 10%. For the other 26% (same number of pathology-based ABMR and non-ABMR), the GS validation results suggested that both pathology and our GS might have their limitations for ABMR diagnosis. Further validation in larger patient cohorts will help clarify the utility of this ABMR GS.
To cite this abstract in AMA style:
Zhang H, Nast CC, Ammerman N, Vo AA, Jordan SC, Toyoda M. Validation of Gene Expression Signatures Associated with Antibody-Mediated Rejection (ABMR) in Renal Allograft Biopsies (Bx) of HLA-Sensitized Patients [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/validation-of-gene-expression-signatures-associated-with-antibody-mediated-rejection-abmr-in-renal-allograft-biopsies-bx-of-hla-sensitized-patients/. Accessed November 22, 2024.« Back to 2019 American Transplant Congress