Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation—Is There Room for Interleukin Profiles?
Imeke Goldschmidt,
Evgeny Chichelnitskiy,
Nicole Rübsamen,
Veronika K. Jaeger,
André Karch,
Lorenzo D’Antiga,
Angelo Di Giorgio,
Emanuele Nicastro,
Deirdre A. Kelly,
Valerie McLin,
Simona Korff,
Dominique Debray,
Muriel Girard,
Loreto Hierro,
Maja Klaudel-Dreszler,
Malgorzata Markiewicz-Kijewska,
Christine Falk,
Ulrich Baumann
Affiliations
Imeke Goldschmidt
Department of Paediatric Liver, Kidney and Metabolic Diseases, Division of Paediatric Gastroenterology and Hepatology, Hannover Medical School, 30625 Hannover, Germany
Evgeny Chichelnitskiy
Institute of Transplant Immunology, Hannover Medical School, 30625 Hannover, Germany
Nicole Rübsamen
Institute of Epidemiology and Social Medicine, University of Münster, 48149 Münster, Germany
Veronika K. Jaeger
Institute of Epidemiology and Social Medicine, University of Münster, 48149 Münster, Germany
André Karch
Institute of Epidemiology and Social Medicine, University of Münster, 48149 Münster, Germany
Lorenzo D’Antiga
Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, 24128 Bergamo, Italy
Angelo Di Giorgio
Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, 24128 Bergamo, Italy
Emanuele Nicastro
Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, 24128 Bergamo, Italy
Deirdre A. Kelly
Liver Unit, Birmingham Children’s Hospital, Birmingham B4 6NH, UK
Valerie McLin
Department Pédiatrie, Services Spécialités Pédiatriques, Hôpitaux Universitaires de Genève, Rue Gabrielle-Perret-Gentil 4, 1211 Genève, Switzerland
Simona Korff
Department Pédiatrie, Services Spécialités Pédiatriques, Hôpitaux Universitaires de Genève, Rue Gabrielle-Perret-Gentil 4, 1211 Genève, Switzerland
Dominique Debray
Pediatric Liver Unit, Department of Paediatric Surgery, Hôpital Necker-Enfants malades, 75015 Paris, France
Muriel Girard
Pediatric Liver Unit, Department of Paediatric Surgery, Hôpital Necker-Enfants malades, 75015 Paris, France
Loreto Hierro
Servicio de Hepatologìa y Transplante, Hospital Infantil Universitario La Paz Madrid, 28046 Madrid, Spain
Maja Klaudel-Dreszler
The Children’s Memorial Health Institute, 04-736 Warszawa, Poland
Malgorzata Markiewicz-Kijewska
The Children’s Memorial Health Institute, 04-736 Warszawa, Poland
Christine Falk
Institute of Transplant Immunology, Hannover Medical School, 30625 Hannover, Germany
Ulrich Baumann
Department of Paediatric Liver, Kidney and Metabolic Diseases, Division of Paediatric Gastroenterology and Hepatology, Hannover Medical School, 30625 Hannover, Germany
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.
