Time-Limited Therapy with Belatacept in Kidney Transplant Recipients

Abstract

Introduction: In kidney transplant recipients, belatacept is usually pursued indefinitely after it has been started. In the setting of the belatacept shortage and after having evaluated the benefit–risk ratio, we established a strategy consisting of time-limited belatacept therapy/transient calcineurin inhibitor withdrawal, whose results are analyzed in that study. Methods: We considered all the kidney transplant recipients that had been switched from conventional immunosuppressive therapy to belatacept and then for whom belatacept has been withdrawn intentionally. Furthermore, in the first 8 patients, we assessed changes in peripheral blood mononuclear cells (PBMC) transcriptome using RNAseq before and 3 months after belatacept withdrawal. Results: Over the study period, 28 out of 94 patients had belatacept intentionally withdrawn including 25 (89%) switched to low-dose CNI. One rejection due to poor compliance occurred. The eGFR after 12 months remained stable from 48 ± 19 mL.1.73 m−2 to 46 ± 17 mL.1.73 m−2 (p = 0.68). However, patients that resumed belatacept/withdrew CNIs (n = 10) had a trend towards a better eGFR comparing with the others (n = 15): 54 ± 20 mL.1.73 m−2 vs. eGFR 43 ± 16 mL.1.73 m−2, respectively (p = 0.15). The only factor associated with belatacept resumption was when the withdrawal took place during the COVID-19 outbreak. Transcriptome analysis of PBMCs, did not support rebound in alloimmune response. Conclusions: These findings underpin the use of belatacept as part of a time-limited therapy, in selected kidney transplant recipients, possibly as an approach to allow efficient vaccination against SARS-CoV-2.

TDG orchestrates ATF4-dependent gene transcription during retinoic acid-induced cell fate acquisition

“…The resulting FASTQ files were analyzed using the 3' Sequencing RNA Profiling (SRP) pipeline (Charpentier et al, 2021). This methodology aligns with previous DGEseq analyses in various studies (Chaumette et al, 2022;Letellier et al, 2022;Ménoret et al, 2023). The SRP pipeline incorporates cutadapt for read trimming and bwa aln (version 0.7.17) for alignment to the mm10 Mus musculus reference genome and transcriptome.…”