PMID- 33025622 OWN - NLM STAT- MEDLINE DCOM- 20210816 LR - 20240330 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 203 IP - 2 DP - 2021 Feb TI - Identification of peripheral CD154(+) T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients. PG - 315-328 LID - 10.1111/cei.13533 [doi] AB - Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate 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 different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were 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, human leukocyte antigen (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 fluorescence activated cell sorter (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 compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4(+) CD154(+) and CD8(+) CD154(+) T cells in parallel with other transplant factors. CI - (c) 2020 British Society for Immunology. FAU - Boix, F AU - Boix F AUID- ORCID: 0000-0002-3926-7920 AD - Haematology Service, University Hospital of Salamanca, Research Biomedical Institute of Salamanca (IBSAL), Salamanca, Spain. FAU - Legaz, I AU - Legaz I AUID- ORCID: 0000-0002-1140-4313 AD - Department of Legal and Forensic Medicine, Faculty of Medicine, Biomedical Research Institute of Murcia (IMIB), Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Murcia, Spain. FAU - Minhas, A AU - Minhas A AD - Clinical Transplantation Laboratory, Barts Health NHS Trust, London, UK. FAU - Alfaro, R AU - Alfaro R AD - Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Jimenez-Coll, V AU - Jimenez-Coll V AD - Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Mrowiec, A AU - Mrowiec A AD - Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Martinez-Banaclocha, H AU - Martinez-Banaclocha H AUID- ORCID: 0000-0003-4421-4740 AD - Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Galian, J A AU - Galian JA AD - Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Botella, C AU - Botella C AD - Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Moya-Quiles, M R AU - Moya-Quiles MR AUID- ORCID: 0000-0003-3677-6372 AD - Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Sanchez-Bueno, F AU - Sanchez-Bueno F AD - Surgery, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Robles, R AU - Robles R AD - Surgery, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - de la Pena-Moral, J AU - de la Pena-Moral J AD - Pathology, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Ramirez, P AU - Ramirez P AD - Surgery, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Pons, J A AU - Pons JA AUID- ORCID: 0000-0001-5017-7240 AD - Digestive Medicine Services, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Minguela, A AU - Minguela A AUID- ORCID: 0000-0003-2472-5893 AD - Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. FAU - Muro, M AU - Muro M AUID- ORCID: 0000-0001-9987-0994 AD - Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201029 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Biomarkers) RN - 0 (HLA-DRB1 Chains) RN - 147205-72-9 (CD40 Ligand) SB - IM MH - Adult MH - Aged MH - Biomarkers/*blood MH - CD4-Positive T-Lymphocytes/immunology MH - CD40 Ligand/*immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Female MH - Flow Cytometry/methods MH - Graft Rejection/*immunology MH - HLA-DRB1 Chains/*immunology MH - Heart Transplantation/methods MH - Humans MH - Liver Transplantation/methods MH - Lymphocyte Activation/immunology MH - Male MH - Middle Aged MH - T-Lymphocyte Subsets/*immunology MH - Transplantation, Homologous/methods MH - Young Adult PMC - PMC7806417 OTO - NOTNLM OT - CD154+ T cells OT - HLA OT - acute cellular rejection OT - cell-mediated immunity (CMI) OT - immunosuppression OT - liver transplantation COIS- Consulting fees and/or non-financial support were reported from Diagnostica Longwood (F. B.), Astellas Pharma S.A. (F. B.) and Rafer (F. B.). The remaining authors certify that they have no competing interests in the subject matter or materials discussed in this manuscript. EDAT- 2020/10/08 06:00 MHDA- 2021/08/17 06:00 PMCR- 2022/02/01 CRDT- 2020/10/07 05:55 PHST- 2020/06/16 00:00 [received] PHST- 2020/09/29 00:00 [revised] PHST- 2020/09/29 00:00 [accepted] PHST- 2020/10/08 06:00 [pubmed] PHST- 2021/08/17 06:00 [medline] PHST- 2020/10/07 05:55 [entrez] PHST- 2022/02/01 00:00 [pmc-release] AID - CEI13533 [pii] AID - 10.1111/cei.13533 [doi] PST - ppublish SO - Clin Exp Immunol. 2021 Feb;203(2):315-328. doi: 10.1111/cei.13533. Epub 2020 Oct 29.