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Identification of peripheral CD154+ T-cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients
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  • Francisco Boix,
  • Isabel Legaz,
  • Alisha Minhas,
  • Rafael Alfaro,
  • Victor Jimenez-Coll,
  • Anna Mrowiec,
  • Helios Martinez-Banaclocha,
  • Jose A. Galian,
  • Carmen Botella,
  • Maria R. Moya-Quiles,
  • Francisco Sanchez-Bueno,
  • Ricardo Robles,
  • Jesus de la Peña-Moral,
  • Pablo Ramirez,
  • Jose A. Pons,
  • Alfredo Minguela,
  • Manuel Muro
Francisco Boix
University Hospital of Salamanca
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Isabel Legaz
University of Murcia Faculty of Medicine
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Alisha Minhas
Hammersmith Hospital
Rafael Alfaro
Virgen de la Arrixaca University Hospital
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Victor Jimenez-Coll
Virgen de la Arrixaca University Hospital
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Anna Mrowiec
Virgen de la Arrixaca University Hospital
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Helios Martinez-Banaclocha
Virgen de la Arrixaca University Hospital
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Jose A. Galian
Virgen de la Arrixaca University Hospital
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Carmen Botella
Virgen de la Arrixaca University Hospital
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Maria R. Moya-Quiles
Virgen de la Arrixaca University Hospital
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Francisco Sanchez-Bueno
Virgen de la Arrixaca University Hospital
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Ricardo Robles
Virgen de la Arrixaca University Hospital
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Jesus de la Peña-Moral
Virgen de la Arrixaca University Hospital
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Pablo Ramirez
Virgen de la Arrixaca University Hospital
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Jose A. Pons
Virgen de la Arrixaca University Hospital
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Alfredo Minguela
Virgen de la Arrixaca University Hospital
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Manuel Muro
Virgen de la Arrixaca University Hospital
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Abstract

Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T-cell subsets participates in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse CD4+CD154+ and CD8+CD154+ T-cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multiparametric flow cytometry functional assay. Thiry patients were immunologically monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+CD154+ and CD8+CD154+ T-cells, HLA mismatch between recipient-donor and their relation with ACR as well as the acute rejection frequencies were analysed. T-cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by FACS analysis. A high percentage of CD4+CD154+ T-cells (p=0.001) and a low percentage of CD8+CD154+ T-cells (p=0.002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+CD154+ (p=0.001) and CD8+CD154+ T-cells (p=0.002). In logistic regression analysis, CD4+CD154+, CD8+CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T-cell subsets were significantly higher in ACR, despite variations compare to pre-transplant. These findings support the selection of candidates for LT based on the pre-transplant percentages of CD4+CD154+ and CD8+CD154+ T-cells in parallel with other transplant factors

Peer review status:Published

02 Jun 2020Submitted to Clinical & Experimental Immunology
05 Jun 2020Submission Checks Completed
05 Jun 2020Assigned to Editor
17 Jun 2020Reviewer(s) Assigned
11 Aug 2020Review(s) Completed, Editorial Evaluation Pending
11 Aug 2020Editorial Decision: Revise Minor
23 Aug 20201st Revision Received
01 Sep 2020Reviewer(s) Assigned
07 Sep 2020Review(s) Completed, Editorial Evaluation Pending
08 Sep 2020Editorial Decision: Revise Minor
29 Sep 20202nd Revision Received
29 Sep 2020Review(s) Completed, Editorial Evaluation Pending
29 Sep 2020Editorial Decision: Accept
29 Oct 2020Published in Clinical & Experimental Immunology. 10.1111/cei.13533