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. 2023 Jan 7;10(1):128.
doi: 10.3390/children10010128.

Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation-Is There Room for Interleukin Profiles?

Imeke Goldschmidt  1 , Evgeny Chichelnitskiy  2 , Nicole Rübsamen  3 , Veronika K Jaeger  3 , André Karch  3 , Lorenzo D'Antiga  4 , Angelo Di Giorgio  4 , Emanuele Nicastro  4 , Deirdre A Kelly  5 , Valerie McLin  6 , Simona Korff  6 , Dominique Debray  7 , Muriel Girard  7 , Loreto Hierro  8 , Maja Klaudel-Dreszler  9 , Malgorzata Markiewicz-Kijewska  9 , Christine Falk  2 , Ulrich Baumann  1
Affiliations

Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation-Is There Room for Interleukin Profiles?

Imeke Goldschmidt et al. Children (Basel). .

Abstract

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.

Keywords: cytokine profile; immune monitoring; liver transplantation; paediatric; rejection.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Volcano plot of soluble cytokine levels in patients with and without rejection. The y-axis represents −1× the logarithmised level of significance, while on the x-axis, the difference between mean concentrations in rejection (rej) and no rejection (no rej) samples is plotted. Cytokines above the blue plotted line had significantly higher values in patients with rejection vs. patients without rejection.
Figure 2
Figure 2
Volcano plot of the correlation of soluble cytokine levels with the degree of acute cellular rejection (correlation coefficient on the x-axis). The y-axis represents the −1× the logarithmised level of significance for each cytokine correlation. −log (p = 0.05) = 1.3.
Figure 3
Figure 3
Calibration curves for the best fitting models. (A) Gradient boosting machine. (B) Elastic net regression.
See this image and copyright information in PMC

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