Core Signature of Rejection-Specific Cytokines and Chemokines in Heart Biopsies After Transplantation

L. M. Radomsky¹, Y. Scheibner², J. F. Kuehne¹, J. Keil¹, K. Beushausen¹, K. Ludmilla², A. Schick², F. Ius², G. Warnecke³, C. Bara², C. S. Falk¹

¹Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany, ²Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany, ³Clinic for Cardiac Surgery, University of Heidelberg, Heidelberg, Germany

Meeting: 2021 American Transplant Congress

Abstract number: 669

Keywords: Biopsy, Heart, Inflammation, Rejection

Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes

Session Information

Session Name: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: Allograft rejection remains one of the limiting factors for survival after HTX. The aim of this project was to characterize the cytokine/chemokine network in heart biopsies and peripheral blood plasma after TX. The quantified cytokine/chemokine concentrations could reflect the ischemia/reperfusion response as well as rejection status of the allograft. Therefore we hypothesize that in heart biopsies with histopathological proven rejection the microenvironment is significantly altered and potentially specific cytokine/chemokine patterns could predict allograft rejection.

*Methods: Heart biopsies (N=181 biopsies; 52 patients) and peripheral blood samples (N=35 patients) were obtained at different time points after HTX. Using luminex-based multiplex assays 50 cytokines/chemokines in tissue lysates and peripheral blood plasma were quantified. Concentrations of samples with rejection and no-rejection were compared in lysates and plasma. Moreover correlation of tissue and plasma levels and comparison of cold static versus normothermic machine preservation were performed.

*Results: With regard to the rejection status we identified significant differences in lysate concentrations. Especially CXCL9/MIG, CXCL4/MIP-1β and CXCL10/IP-10 showed significantly elevated concentrations in biopsies with proven rejection (p<0.001). In addition, we identified individual long-term changes of single patients after transplantation and significant differences comparing tissue lysates with plasma concentrations. Interestingly, we found no strong correlation between plasma and lysate concentrations. Moreover significantly elevated concentrations of MIF, M-CSF, FGF basic and ICAM-1 (p<0.05) in the first biopsies after HTX were found by comparing cold static preservation and normothermic machine perfusion.

*Conclusions: We could detect a core signature for biopsies with pathologically secured rejection consisting of increased concentrations of the chemokines CXCL9/MIG, CXCL3/ MIP-1α, CXCL4/MIP-1β and CXCL10/IP-10. This signature is clearly distinguished from the pattern of the ischemia/reperfusion response (i.e. elevated levels of IL-6, CXCL8, IL-10) suggesting differences in the underlying inflammatory mechanisms. Importantly, since there was no correlation between the measured protein concentrations in plasma and tissue lysates, biopsies remain indispensable for the diagnosis of heart rejection.

To cite this abstract in AMA style:

Radomsky LM, Scheibner Y, Kuehne JF, Keil J, Beushausen K, Ludmilla K, Schick A, Ius F, Warnecke G, Bara C, Falk CS. Core Signature of Rejection-Specific Cytokines and Chemokines in Heart Biopsies After Transplantation [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/core-signature-of-rejection-specific-cytokines-and-chemokines-in-heart-biopsies-after-transplantation/. Accessed June 1, 2025.

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