An Orchestrated Sequence of Innate and Adaptive Immune Responses Is Associated With Rejection After Pediatric Liver Transplantation

C. Falk,¹ I. Goldschmidt,² F. Mutschler,² C. Neudörfl,¹ J. Keil,¹ K. Daemen,¹ F. Lehner,³ R. Mikolajzcyk,⁴ A. Karch,⁴ U. Baumann.²

¹Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany
²Division of Pediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
³Department of Visceral General and Transplant Surgery, Hannover Medical School, Hannover, Germany
⁴Department of Epidemiology, Helmholtz Center for Infection Research, HZI, Braunschweig, Braunschweig, Germany.

Meeting: 2015 American Transplant Congress

Abstract number: D84

Keywords: Inflammation, Liver transplantation, Pediatric, Rejection

Session Information

Session Name: Poster Session D: Innate Immunity in Transplantation

Session Type: Poster Session

Date: Tuesday, May 5, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

The concept of a coordinated immune response initiated by innate and 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. In addition, the impact of immunosuppression on this scenario has not been defined in detail, especially not for pediatric liver transplantation. Therefore, we aimed to demonstrate that an orchestrated sequence of innate and adaptive immune reactions can be defined in children after liver transplantation and that these immune patterns can be correlated with clinical parameters.

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-12, sCD25, TRAIL and NK cells was identified in >50% of patients (pattern 1). 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 and tissue factors like HGF (pattern 2), a clinically relevant rejection episode was found to be associated in form of biopsy-proven acute rejection (PBAR). In contrast, if all cellular and soluble parameters remained silent (pattern 3), this non-reactive status was associated with a stable transplant which was presumably achieved by sufficient immunosuppressive treatment.

Conclusion: 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 rejection and enable to identify markers that allow optimization of immunosuppression..

To cite this abstract in AMA style:

Falk C, Goldschmidt I, Mutschler F, Neudörfl C, Keil J, Daemen K, Lehner F, Mikolajzcyk R, Karch A, Baumann U. An Orchestrated Sequence of Innate and Adaptive Immune Responses Is Associated With Rejection After Pediatric Liver Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/an-orchestrated-sequence-of-innate-and-adaptive-immune-responses-is-associated-with-rejection-after-pediatric-liver-transplantation/. Accessed May 19, 2025.

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