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DSA Are Associated With More Graft Injury, More Fibrosis, and Upregulation of Rejection-associated Transcripts in Subclinical Rejection.

Abstract：

BACKGROUND:Subclinical T cell-mediated rejection (subTCMR) is commonly found after liver transplantation and has a good short-term prognosis, even when it is left untreated. Donor-specific antibodies (DSA) are putatively associated with a worse prognosis for recipient and graft after liver transplantation. METHODS:To assess the immune regulation in subTCMR grafts, gene expression of 93 transcripts for graft injury, tolerance, and immune regulation was analyzed in 77 biopsies with "no histologic rejection" (NHR; n = 25), "clinical TCMR" (cTMCR; n = 16), and subTCMR (n = 36). In addition, all available subTCMR biopsies (n = 71) were tested for DSA with bead assays. RESULTS:SubTCMR showed heterogeneous and intermediate expression profiles of transcripts that were upregulated in cTCMR. Graft gene expression suggested a lower activation of effector lymphocytes and a higher activation of regulatory T cells in grafts with subTCMR compared to cTCMR. DSA positivity in subTCMR was associated with histological evidence of more severe graft inflammation and fibrosis. This more severe DSA+ associated graft injury in subTCMR was converged with an upregulation of cTCMR-associated transcripts. In nonsupervised analysis, DSA positive subTCMR mostly clustered together with cTCMR, while DSA negative subTCMR clustered together with NHR. CONCLUSIONS:T cell-mediated rejection seems to form a continuum of alloimmune activation. Although subTCMR exhibited less expression of TCMR-associated transcript, DSA positivity in subTCMR was associated with an upregulation of rejection-associated transcripts. The identification of DSA positive subclinical rejection might help to define patients with more inflammation in the graft and development of fibrosis.

journal_name

Transplantation

journal_title

Transplantation

authors

Höfer A,Jonigk D,Hartleben B,Verboom M,Hallensleben M,Hübscher SG,Manns MP,Jaeckel E,Taubert R

doi

10.1097/TP.0000000000003034

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

551-561

issue

eissn

0041-1337

issn

1534-6080

pii

00007890-202003000-00022

journal_volume

104

pub_type

杂志文章

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DSA Are Associated With More Graft Injury, More Fibrosis, and Upregulation of Rejection-associated Transcripts in Subclinical Rejection.