DSA are associated with more graft injury, more fibrosis and upregulation of rejection associated transcripts in subclinical rejection.
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Authors
Höfer, AnneJonigk, Danny
Hartleben, Björn
Verboom, Murielle
Hallensleben, Michael
Hübscher, Stefan G
Manns, Michael P

Jaeckel, Elmar
Taubert, Richard
Issue Date
2019-10-23
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Show full item recordAbstract
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 histological 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. Conclusion: T cell-mediated rejection seem 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.Citation
Transplantation. 2019 Oct 23. doi: 10.1097/TP.0000000000003034.Affiliation
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.Publisher
Lippincott, Williams & WilkinsJournal
TransplantationPubMed ID
31651790Type
ArticleLanguage
enISSN
1534-6080ae974a485f413a2113503eed53cd6c53
10.1097/TP.0000000000003034
Scopus Count
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