Background: Multiple molecular signatures specific to ABMR based on gene expression in renal allograft Bx of transplant recipients were reported. Here we assessed mRNA transcript profiles of 3 ABMR-specific gene combination established by our group in renal allograft Bx of HLA-sensitized patient desensitized with IVIG+rituximab+IdeS prior to kidney transplantation.

Methods: Total RNA was extracted from 20 Bx (2 ABMR [including borderline ABMR {bABMR}], 7 ABMR+CMR [including bABMR+bCMR], 5 CMR [including bCMR], 6 no rejection Control [NR]) from 13 patients for reverse transcription, pre-amplification and qPCR. All 20 Bx were obtained within 13 months post-transplant. 5 patients had 2 or 3 Bx at different time points. 3 ABMR-associated genes (CCL3, SH2D1B and KLRF1) identified in our previous Bx gene expression study were examined. The expression levels of each gene were presented as relative quantity (RQ) vs. a reference RNA after normalized by housekeeping GAPDH gene. Gene scores (GS) were calculated based on the RQ of these 3 genes in each Bx for further comparison.

Results: Among 20 Bx, 11 showed higher GS (2.30±2.94), while the remaining 9 showed lower GS (0.19±0.16). Among 11 Bx with higher GS, 8 were ABMR/bABMR, ABMR+CMR or bABMR+bCMR, while the remaining 3 had NR diagnosis. However, these 3 Bx with NR diagnosis were obtained from 2 patients both of whom had additional bABMR+CMR Bx with higher GS in this study, suggesting that both patients might have ongoing ABMR/bABMR despite NR diagnosis in Bx. Among 9 Bx with lower GS, 8 had either NR or CMR/bCMR diagnosis, while 1 was diagnosed as bABMR+CMR. This bABMR+CMR Bx with low GS was obtained from a patient who had another CMR Bx with low GS 6 months earlier, suggesting that this low GS bABMR+CMR Bx may be CMR only without bABMR.

Conclusions: Monitoring mRNA transcript levels of 3 genes (CCL3, SH2D1B and KLRF1) in renal allograft Bx may provide additional information related to the rejection status and help to distinguish ABMR from others in histopathologic diagnosis for renal allograft Bx.

CITATION INFORMATION: Zhang H., Nast C., Doldron J., Cheung M., Vo A., Jordan S., Toyoda M. mRNA Transcript Profiling of 3 Genes in Renal Allograft Biopsies (Bx) Improves Accuracy of Antibody-Mediated Rejection (ABMR) Diagnosis in Transplant Recipients Desensitized with IVIG+Rituximab+Immunoglobulin G-Degrading Enzyme of Streptococcus Pyogenes (IdeS) Am J Transplant. 2017;17 (suppl 3).

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