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Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation—Is There Room for Interleukin Profiles?
Background: The current gold standard to diagnose T-cell-mediated acute rejection (TCMR) requires liver histology. Using data from the ChilSFree study on immune response after paediatric liver transplantation (pLT), we aimed to assess whether soluble cytokines can serve as an alternative diagnostic...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857115/ https://www.ncbi.nlm.nih.gov/pubmed/36670678 http://dx.doi.org/10.3390/children10010128 |
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author | Goldschmidt, Imeke Chichelnitskiy, Evgeny Rübsamen, Nicole Jaeger, Veronika K. Karch, André D’Antiga, Lorenzo Di Giorgio, Angelo Nicastro, Emanuele Kelly, Deirdre A. McLin, Valerie Korff, Simona Debray, Dominique Girard, Muriel Hierro, Loreto Klaudel-Dreszler, Maja Markiewicz-Kijewska, Malgorzata Falk, Christine Baumann, Ulrich |
author_facet | Goldschmidt, Imeke Chichelnitskiy, Evgeny Rübsamen, Nicole Jaeger, Veronika K. Karch, André D’Antiga, Lorenzo Di Giorgio, Angelo Nicastro, Emanuele Kelly, Deirdre A. McLin, Valerie Korff, Simona Debray, Dominique Girard, Muriel Hierro, Loreto Klaudel-Dreszler, Maja Markiewicz-Kijewska, Malgorzata Falk, Christine Baumann, Ulrich |
author_sort | Goldschmidt, Imeke |
collection | PubMed |
description | Background: The current gold standard to diagnose T-cell-mediated acute rejection (TCMR) requires liver histology. Using data from the ChilSFree study on immune response after paediatric liver transplantation (pLT), we aimed to assess whether soluble cytokines can serve as an alternative diagnostic tool in children suspected to have TCMR. Methods: A total of n = 53 blood samples obtained on the day of or up to 3 days before liver biopsy performed for suspected TCMR at median 18 days (range 7–427) after pLT in n = 50 children (38% female, age at pLT 1.8 (0.5–17.5) years) were analysed for circulating cytokine levels using Luminex-based Multiplex technology. Diagnostic accuracy of cytokine concentrations was assessed using a multivariable model based on elastic net regression and gradient boosting machine analysis. Results: TCMR was present in 68% of biopsies. There was strong evidence that patients with TCMR had increased levels of soluble CXCL8, CXCL9, CXCL10, IL-16, IL-18, HGF, CCL4, MIF, SCGF-β, and HGF before biopsy. There was some evidence for increased levels of sCD25, ICAM-1, IL-6, IL-3, and CCL11. Diagnostic value of both single cytokine levels and a combination of cytokines and clinical markers was poor, with AUROCs not exceeding 0.7. Conclusion: Patients with TCMR showed raised levels of cytokines and chemokines reflective of T-cell activation and chemotaxis. Despite giving insight into the mechanisms of TCMR, the diagnostic value of soluble cytokines for the confirmation of TCMR in a clinical scenario of suspected TCMR is poor. |
format | Online Article Text |
id | pubmed-9857115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98571152023-01-21 Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation—Is There Room for Interleukin Profiles? Goldschmidt, Imeke Chichelnitskiy, Evgeny Rübsamen, Nicole Jaeger, Veronika K. Karch, André D’Antiga, Lorenzo Di Giorgio, Angelo Nicastro, Emanuele Kelly, Deirdre A. McLin, Valerie Korff, Simona Debray, Dominique Girard, Muriel Hierro, Loreto Klaudel-Dreszler, Maja Markiewicz-Kijewska, Malgorzata Falk, Christine Baumann, Ulrich Children (Basel) Article Background: The current gold standard to diagnose T-cell-mediated acute rejection (TCMR) requires liver histology. Using data from the ChilSFree study on immune response after paediatric liver transplantation (pLT), we aimed to assess whether soluble cytokines can serve as an alternative diagnostic tool in children suspected to have TCMR. Methods: A total of n = 53 blood samples obtained on the day of or up to 3 days before liver biopsy performed for suspected TCMR at median 18 days (range 7–427) after pLT in n = 50 children (38% female, age at pLT 1.8 (0.5–17.5) years) were analysed for circulating cytokine levels using Luminex-based Multiplex technology. Diagnostic accuracy of cytokine concentrations was assessed using a multivariable model based on elastic net regression and gradient boosting machine analysis. Results: TCMR was present in 68% of biopsies. There was strong evidence that patients with TCMR had increased levels of soluble CXCL8, CXCL9, CXCL10, IL-16, IL-18, HGF, CCL4, MIF, SCGF-β, and HGF before biopsy. There was some evidence for increased levels of sCD25, ICAM-1, IL-6, IL-3, and CCL11. Diagnostic value of both single cytokine levels and a combination of cytokines and clinical markers was poor, with AUROCs not exceeding 0.7. Conclusion: Patients with TCMR showed raised levels of cytokines and chemokines reflective of T-cell activation and chemotaxis. Despite giving insight into the mechanisms of TCMR, the diagnostic value of soluble cytokines for the confirmation of TCMR in a clinical scenario of suspected TCMR is poor. MDPI 2023-01-07 /pmc/articles/PMC9857115/ /pubmed/36670678 http://dx.doi.org/10.3390/children10010128 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Goldschmidt, Imeke Chichelnitskiy, Evgeny Rübsamen, Nicole Jaeger, Veronika K. Karch, André D’Antiga, Lorenzo Di Giorgio, Angelo Nicastro, Emanuele Kelly, Deirdre A. McLin, Valerie Korff, Simona Debray, Dominique Girard, Muriel Hierro, Loreto Klaudel-Dreszler, Maja Markiewicz-Kijewska, Malgorzata Falk, Christine Baumann, Ulrich Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation—Is There Room for Interleukin Profiles? |
title | Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation—Is There Room for Interleukin Profiles? |
title_full | Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation—Is There Room for Interleukin Profiles? |
title_fullStr | Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation—Is There Room for Interleukin Profiles? |
title_full_unstemmed | Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation—Is There Room for Interleukin Profiles? |
title_short | Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation—Is There Room for Interleukin Profiles? |
title_sort | diagnosing acute cellular rejection after paediatric liver transplantation—is there room for interleukin profiles? |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857115/ https://www.ncbi.nlm.nih.gov/pubmed/36670678 http://dx.doi.org/10.3390/children10010128 |
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