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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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