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Biopsy-Proven Rejection in Children After Liver Transplantation Is Associated by an IL-12p40-Mediated Innate Immune Response Followed by Th1 T Cell Activation.

C. Falk,1 I. Goldschmidt,2 F. Mutschler,2 E. Pfister,2 F. Lehner,3 J. Keil,1 C. Neudörfl,1 A. Karch,4 R. Mikolajczyk,4 U. Baumann.2

1Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Bitte Wählen, Germany
2Department of Pediatric Hepatology, Hannover Medical School, Hannover, Bitte Wählen, Germany
3Department of Abdominal and Transplantation Surgery, Hannover Medical School, Hannover, Bitte Wählen, Germany
4Department of Epidemiology, Helmholtz Center for Infection Research, HZI, Braunschweig, Germany.

Meeting: 2016 American Transplant Congress

Abstract number: D220

Keywords: Immunogenicity, Liver transplantation

Session Information

Session Name: Poster Session D: Pediatric Liver Transplantation

Session Type: Poster Session

Date: Tuesday, June 14, 2016

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Halls C&D

Sustained by adaptive immune cells and their soluble mediators is well established for infection but it has not been demonstrated for solid organ transplantation in humans. Therefore, we wanted to identify a sequence of innate and adaptive immune reactions in children after liver transplantation that correlated with rejection as clinical outcome.

Subjects and methods: In the frame of the CHILSFree study, 32 children, aged 3 months to 16 years, were liver transplanted at MHH for end stage liver disease. Lymphocyte subsets as well as cytokines and chemokines in peripheral blood were quantified by flow cytometry and multiplex technique before, weekly up to 4 weeks after LTx.

Results: Three major patterns could be identified among T, B and NK cell subsets correlating with their respective cytokines and chemokines. A first innate response wave by IL-12p40, sCD25, TRAIL and NK cells was identified in 50% of patients. However, only if this 1st wave was followed by a 2nd wave of adaptive response, i.e. T cell expansion and elevated levels of IFN-g, IL-1RA, IL-13, IL-17, CCL5 and CXCL10, clinically relevant rejection was associated in form of biopsy-proven acute rejection (PBAR). In contrast, if all cellular and soluble parameters remained silent, this non-reactive status was associated with a stable transplant which was presumably achieved by sufficient immunosuppressive treatment.

Conclusion: The quantification of a panel of cellular and soluble immune markers during the first weeks after pediatric liver Tx may provide relevant information for an early detection of the risk of rejection and enable us to identify markers that allow an optimization of immunosuppressive treatment.

CITATION INFORMATION: Falk C, Goldschmidt I, Mutschler F, Pfister E, Lehner F, Keil J, Neudörfl C, Karch A, Mikolajczyk R, Baumann U. Biopsy-Proven Rejection in Children After Liver Transplantation Is Associated by an IL-12p40-Mediated Innate Immune Response Followed by Th1 T Cell Activation. Am J Transplant. 2016;16 (suppl 3).

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To cite this abstract in AMA style:

Falk C, Goldschmidt I, Mutschler F, Pfister E, Lehner F, Keil J, Neudörfl C, Karch A, Mikolajczyk R, Baumann U. Biopsy-Proven Rejection in Children After Liver Transplantation Is Associated by an IL-12p40-Mediated Innate Immune Response Followed by Th1 T Cell Activation. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/biopsy-proven-rejection-in-children-after-liver-transplantation-is-associated-by-an-il-12p40-mediated-innate-immune-response-followed-by-th1-t-cell-activation/. Accessed May 11, 2025.

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