Identification of a Unique and Mechanistic Urinary Cell mRNA Signature in Tolerant Kidney Transplant Recipients Conditioned with FCR001 Facilitating Cells

J. Lee¹, J. R. Leventhal², C. Li³, R. Ding¹, S. Ildstad⁴, M. Suthanthiran⁵

¹Weill Cornell Medicine, New York, NY, ²Surgery, Northwestern Medicine, Chicago, IL, ³Medicine, WCMC, New York, NY, ⁴Univ Louisville / Talaris, Louisville, KY, ⁵Weill Cornell Med, New York, NY

Meeting: 2022 American Transplant Congress

Abstract number: 173

Keywords: Gene expression, Kidney transplantation, Tolerance

Topic: Basic Science » Basic Science » 12 - Immunosuppression & Tolerance: Preclinical & Translational Studies

Session Information

Session Name: Immunosuppression and Tolerance: Preclinical and Translational Studies

Session Type: Rapid Fire Oral Abstract

Date: Sunday, June 5, 2022

Session Time: 5:30pm-7:00pm

Presentation Time: 6:30pm-6:40pm

Location: Hynes Ballroom A

*Purpose: Urinary cell mRNA profiling is a powerful tool to interrogate kidney allograft status and can diagnose and anticipate acute rejection in kidney allograft recipients. In this study, we seek to identify a urinary cell mRNA signature in tolerant KTx recipients conditioned with FCR001 facilitating cells and correlate it with donor chimerism.

*Methods: We measured a hypothesis-based custom panel of urinary cell mRNAs in 28 biopsy-matched urine specimens from 14 FCR001-tolerant pts with durable chimerism, normal biopsy features and off immunosuppression (FCR Durable Cohort) and compared the urinary mRNA profile to two standard-of-care cohorts from the Clinical Trials in Organ Transplantation -04 (CTOT-04) study: 43 biopsy-matched urine specimens from 34 KTx recipients with biopsies with acute cellular rejection (TCMR Cohort) and 161 biopsy-matched urine specimens from 124 KTx recipients with biopsies without acute or chronic rejection features (No Rejection Cohort).

*Results: The FCR Durable Cohort had higher urinary cell mRNA copies of CTLA-4 than the TCMR Cohort (median copy number: 439 CTLA-4 per microgram of RNA vs. 135 per microgram of RNA, P=0.005) as well as higher copy number than in the No Rejection Cohort (439 vs. 13, P = 6×10^-15). A ratio of CTLA-4 mRNA to granzyme B mRNA was higher in the FCR Durable Cohort than the TCMR Cohort (5.62 vs. 0.03, P=6 x10^-16) and also higher than in the No Rejection Cohort (5.62 vs. 0.04, P=7×10^-15). The FCR Durable Cohort had lower urinary cell mRNA copies of CD3e, granzyme B, perforin, IP-10, FoxP3, TGF-b1 and 18S rRNA than the TCMR Cohort (P<0.05, Wilcoxon rank sum test). The FCR Durable Cohort had similar levels of urinary cell mRNA for CD3e, perforin, IP-10 and FoxP3 to the No Rejection Cohort (P>0.05) and lower levels of urinary cell mRNA for granzyme B and TGF-b1 than the No Rejection Cohort (P<0.05). The CTLA-4 mRNA to granzyme B mRNA ratio was numerically higher in the FCR Durable Cohort (28 urine specimens from 14 pts) than in the FCR Transient Group (11 urine specimens from 3 pts) (5.62 vs. 1.99, P=0.21). The Figure shows box and whisker plots for the urinary cell mRNA genes by cohort with Kruskal-Wallis p-values

*Conclusions: We have identified a unique and mechanistic urinary mRNA tolerance signature, defined by the ratio of CTLA-4 to granzyme B mRNA, in tolerant kidney allograft recipients which is consistent with immune quiescence.”

To cite this abstract in AMA style:

Lee J, Leventhal JR, Li C, Ding R, Ildstad S, Suthanthiran M. Identification of a Unique and Mechanistic Urinary Cell mRNA Signature in Tolerant Kidney Transplant Recipients Conditioned with FCR001 Facilitating Cells [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/identification-of-a-unique-and-mechanistic-urinary-cell-mrna-signature-in-tolerant-kidney-transplant-recipients-conditioned-with-fcr001-facilitating-cells/. Accessed November 21, 2024.

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