A plasmatic score using a miRNA signature and CXCL-10 for accurate prediction and diagnosis of liver allograft rejection
IntroductionThe use of noninvasive biomarkers may avoid the need for liver biopsy (LB) and could guide immunosuppression adjustment in liver transplantation (LT). The aims of this study were: to confirm the predictive and diagnostic capacity of plasmatic expression of miR-155-5p, miR-181a-5p, miR-12...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1196882/full |
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| author | Olga Millán Olga Millán Pablo Ruiz Judit Julian Judit Julian Ana Lizana Yiliam Fundora Yiliam Fundora Gonzalo Crespo Gonzalo Crespo Jordi Colmenero Jordi Colmenero Miquel Navasa Miquel Navasa Mercè Brunet Mercè Brunet |
| author_facet | Olga Millán Olga Millán Pablo Ruiz Judit Julian Judit Julian Ana Lizana Yiliam Fundora Yiliam Fundora Gonzalo Crespo Gonzalo Crespo Jordi Colmenero Jordi Colmenero Miquel Navasa Miquel Navasa Mercè Brunet Mercè Brunet |
| author_sort | Olga Millán |
| collection | DOAJ |
| description | IntroductionThe use of noninvasive biomarkers may avoid the need for liver biopsy (LB) and could guide immunosuppression adjustment in liver transplantation (LT). The aims of this study were: to confirm the predictive and diagnostic capacity of plasmatic expression of miR-155-5p, miR-181a-5p, miR-122-5p and CXCL-10 for assessing T-cell mediated rejection (TCMR) risk; to develop a score based on a panel of noninvasive biomarkers to predict graft rejection risk and to validate this score in a separate cohort.MethodsA prospective, observational study was conducted with a cohort of 79 patients followed during the first year after LT. Plasma samples were collected at predetermined time points for the analysis of miRNAs and the CXCL-10. Patients with LFTs abnormalities were submitted to a LB to rule out rejection, assessing previous and concurrent expression of the biomarkers to evaluate their predictive and diagnostic ability. Information from 86 patients included in a previous study was collected and used as a validation cohort.ResultsTwenty-four rejection episodes were diagnosed in 22 patients. Plasmatic CXCL-10 concentration and the expression of the three miRNAs were significantly elevated prior to and at the moment of the diagnosis of rejection. We developed a logistic model for rejection prediction and diagnosis, which included CXCL-10, miR-155-5p and miR-181a-5p. The area under the ROC curve (AUROC) for rejection prediction was 0.975 (79.6% sensitivity, 99.1% specificity, 90,7% PPV; 97.7% NPV; 97.1% correctly classified) and 0.99 for diagnosis (87.5% sensitivity, 99.5% specificity, 91.3% PPV; 99.3% NPV; 98.9% correctly classified). In the validation cohort (n=86; 14 rejections), the same cut-off points were used obtaining AUROCs for rejection prediction and diagnosis of 0.89 and 0.92 respectively. In patients with graft dysfunction in both cohorts the score could discriminate those with rejection regarding other causes with an AUROC of 0.98 (97.3% sensitivity, 94.1%specificity).ConclusionThese results suggest that the clinical implementation of the monitoring of this noninvasive plasmatic score may allow the prediction and diagnosis of rejection and identify patients with graft dysfunction due to rejection, helping with a more efficient guide for immunosuppressive therapy adjustment. This finding warrants the development of prospective biomarker-guided clinical trials. |
| first_indexed | 2024-03-13T08:18:57Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T08:18:57Z |
| publishDate | 2023-05-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-af6700a1eae642808d0bd4199c0be5f02023-05-31T11:01:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11968821196882A plasmatic score using a miRNA signature and CXCL-10 for accurate prediction and diagnosis of liver allograft rejectionOlga Millán0Olga Millán1Pablo Ruiz2Judit Julian3Judit Julian4Ana Lizana5Yiliam Fundora6Yiliam Fundora7Gonzalo Crespo8Gonzalo Crespo9Jordi Colmenero10Jordi Colmenero11Miquel Navasa12Miquel Navasa13Mercè Brunet14Mercè Brunet15Biomedical Research Center in Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III (ISCII), Madrid, SpainPharmacology and Toxicology, Biochemistry and Molecular Genetics, Biomedical Diagnostic Center (CDB), Hospital Clinic of Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, SpainLiver Unit, Hospital Clinic of Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, SpainPharmacology and Toxicology, Biochemistry and Molecular Genetics, Biomedical Diagnostic Center (CDB), Hospital Clinic of Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, SpainBiochemistry and Molecular Genetics, Biomedical Diagnostic Center, Hospital Clínic of Barcelona, Barcelona, SpainPharmacology and Toxicology, Biochemistry and Molecular Genetics, Biomedical Diagnostic Center (CDB), Hospital Clinic of Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, SpainBiomedical Research Center in Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III (ISCII), Madrid, SpainDepartment of General and Digestive Surgery, Hospital Clínic Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, SpainBiomedical Research Center in Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III (ISCII), Madrid, SpainLiver Unit, Hospital Clinic of Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, SpainBiomedical Research Center in Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III (ISCII), Madrid, SpainLiver Unit, Hospital Clinic of Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, SpainBiomedical Research Center in Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III (ISCII), Madrid, SpainLiver Unit, Hospital Clinic of Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, SpainBiomedical Research Center in Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III (ISCII), Madrid, SpainPharmacology and Toxicology, Biochemistry and Molecular Genetics, Biomedical Diagnostic Center (CDB), Hospital Clinic of Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, SpainIntroductionThe use of noninvasive biomarkers may avoid the need for liver biopsy (LB) and could guide immunosuppression adjustment in liver transplantation (LT). The aims of this study were: to confirm the predictive and diagnostic capacity of plasmatic expression of miR-155-5p, miR-181a-5p, miR-122-5p and CXCL-10 for assessing T-cell mediated rejection (TCMR) risk; to develop a score based on a panel of noninvasive biomarkers to predict graft rejection risk and to validate this score in a separate cohort.MethodsA prospective, observational study was conducted with a cohort of 79 patients followed during the first year after LT. Plasma samples were collected at predetermined time points for the analysis of miRNAs and the CXCL-10. Patients with LFTs abnormalities were submitted to a LB to rule out rejection, assessing previous and concurrent expression of the biomarkers to evaluate their predictive and diagnostic ability. Information from 86 patients included in a previous study was collected and used as a validation cohort.ResultsTwenty-four rejection episodes were diagnosed in 22 patients. Plasmatic CXCL-10 concentration and the expression of the three miRNAs were significantly elevated prior to and at the moment of the diagnosis of rejection. We developed a logistic model for rejection prediction and diagnosis, which included CXCL-10, miR-155-5p and miR-181a-5p. The area under the ROC curve (AUROC) for rejection prediction was 0.975 (79.6% sensitivity, 99.1% specificity, 90,7% PPV; 97.7% NPV; 97.1% correctly classified) and 0.99 for diagnosis (87.5% sensitivity, 99.5% specificity, 91.3% PPV; 99.3% NPV; 98.9% correctly classified). In the validation cohort (n=86; 14 rejections), the same cut-off points were used obtaining AUROCs for rejection prediction and diagnosis of 0.89 and 0.92 respectively. In patients with graft dysfunction in both cohorts the score could discriminate those with rejection regarding other causes with an AUROC of 0.98 (97.3% sensitivity, 94.1%specificity).ConclusionThese results suggest that the clinical implementation of the monitoring of this noninvasive plasmatic score may allow the prediction and diagnosis of rejection and identify patients with graft dysfunction due to rejection, helping with a more efficient guide for immunosuppressive therapy adjustment. This finding warrants the development of prospective biomarker-guided clinical trials.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1196882/fullnoninvasive biomarkersscoremiRNAsCXCL-10liver transplant (LT)rejection |
| spellingShingle | Olga Millán Olga Millán Pablo Ruiz Judit Julian Judit Julian Ana Lizana Yiliam Fundora Yiliam Fundora Gonzalo Crespo Gonzalo Crespo Jordi Colmenero Jordi Colmenero Miquel Navasa Miquel Navasa Mercè Brunet Mercè Brunet A plasmatic score using a miRNA signature and CXCL-10 for accurate prediction and diagnosis of liver allograft rejection Frontiers in Immunology noninvasive biomarkers score miRNAs CXCL-10 liver transplant (LT) rejection |
| title | A plasmatic score using a miRNA signature and CXCL-10 for accurate prediction and diagnosis of liver allograft rejection |
| title_full | A plasmatic score using a miRNA signature and CXCL-10 for accurate prediction and diagnosis of liver allograft rejection |
| title_fullStr | A plasmatic score using a miRNA signature and CXCL-10 for accurate prediction and diagnosis of liver allograft rejection |
| title_full_unstemmed | A plasmatic score using a miRNA signature and CXCL-10 for accurate prediction and diagnosis of liver allograft rejection |
| title_short | A plasmatic score using a miRNA signature and CXCL-10 for accurate prediction and diagnosis of liver allograft rejection |
| title_sort | plasmatic score using a mirna signature and cxcl 10 for accurate prediction and diagnosis of liver allograft rejection |
| topic | noninvasive biomarkers score miRNAs CXCL-10 liver transplant (LT) rejection |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1196882/full |
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