Z Gastroenterol 2022; 60(08): e484
DOI: 10.1055/s-0042-1754738
Abstracts | DGVS/DGAV
Leber und Galle
Leberzirrhose: Grundlagen II
Donnerstag, 15. September 2022, 10:10 – 11:14, Saal 5

Genes of the coagulation and innate immune system cascade are potentially involved in hepatic graft versus host disease (GvHD) after transcriptomic profiling

Authors

  • Y Qian

    1   Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Section of Hepatology, Mannheim, Deutschland

  • K Evert

    2   University of Regensburg, Germany, Department of Pathology, Regensburg, Deutschland

  • T Itzel

    1   Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Section of Hepatology, Mannheim, Deutschland

  • JE Albin

    1   Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Section of Hepatology, Mannheim, Deutschland

  • E Kallinowski

    1   Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Section of Hepatology, Mannheim, Deutschland

  • M Neubauer

    1   Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Section of Hepatology, Mannheim, Deutschland

  • MP Ebert

    1   Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Section of Hepatology, Mannheim, Deutschland

  • W Herr

    3   University Medical Center, Regensburg, Germany, Department of Medicine III, Regensburg, Deutschland

  • M Evert

    2   University of Regensburg, Germany, Department of Pathology, Regensburg, Deutschland

  • NM Meindl-Beinker

    1   Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Section of Hepatology, Mannheim, Deutschland

  • A Dropmann

    1   Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Section of Hepatology, Mannheim, Deutschland

  • M Edinger

    3   University Medical Center, Regensburg, Germany, Department of Medicine III, Regensburg, Deutschland

  • E Holler

    3   University Medical Center, Regensburg, Germany, Department of Medicine III, Regensburg, Deutschland

  • A Teufel

    1   Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Section of Hepatology, Mannheim, Deutschland
Further Information
Also available at
 
 

Background and aims Graft-versus-host-disease (GvHD) is a common complication following allogeneic hematopoietic stem cell transplantation (aHCT) that typically manifests as injury response to the skin, gastrointestinal mucosa and liver. In liver, late onset acute and chronic liver GvHD are more similar to an autoimmune reaction. The identification of valid GvHD biomarker is still an unmet clinical need. In our study, we therefore aimed to identify gene expression patterns, which could be used as potential indicators for the outcome of aHCTs with regard to acute or chronic GvHD. For this purpose, we expect to uncover similar and distinct gene signatures of GvHD in comparison to non-diseased liver tissues and detect potential candidates giving information about the outcome after aHCT.

Method Microarray analyses from FFPE samples of patients were performed, and the following criteria were applied: fold change> [1] and a p- value<0,05. Gene expression datasets were compared comprising livers from GvHD, AIH (autoimmune hepatitis) and healthy individuals. Candidate selection and functional annotation analyses were done using Webgestalt or DAVID. Experimental validation of target genes in tissues of GvHD and non-diseased patients was performed by immunohistochemistry, qPCR, immunoblot and RNAscope. Further validation and characterization were done based on public collective data for aGvHD and inflammatory hepatopathies.

Results Evaluation of microarray data revealed 388 (out of 19526) regulated genes in hepatic GvHD.Functional annotation analysis indicated gene expression cluster of the complement and coagulation cascades as well as the innate immune system. Comparing these clusters, 72 overlapping genes were found in GvHD and AIH. Among these, strongest regulation was found in ten genes from which we selected SERPINF2 and CPN1 for experimental validation in patient tissues. We could at least partly confirm the abundance and regulation of the selected targets in tissues of GvHD and non-diseased livers in which CPN1 shows upregulation in GvhD but repression in healthy individuals while SerpinF2 regulation shows the opposite response.

Conclusion We provide a first molecular characterization of GvHD in the liver. GvHD showed common regulation with other AIHs but also distinct features. SERPINF2 and CPN1 were promising candidates for further experimental and functional analyses.


Publication History

Article published online:
19 August 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany