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Epithelial barrier dysfunction as permissive pathomechanism in human intestinal graft-versus-host disease

Bone Marrow Transplantation volume 53, pages 1083–1086 (2018)Cite this article

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Acute graft-versus-host disease (A-GVHD) is characterized by a strong inflammatory reaction of the graft against the recipient, mainly in the skin, the intestine and the liver. The gastrointestinal manifestation of the disease is characterized by nausea, vomiting, abdominal cramps and diarrhea with extensive fluid loss. Histologically, diagnosis of A-GVHD in colonic biopsies is characterized by crypt abscesses and epithelial apoptosis [1]. Pathophysiologically, A-GVHD is described as a three-stage model with activation of antigen presenting cells in the host, donor T-cell activation and target tissue destruction [2]. Within this model barrier dysfunction with translocation of microbial products and luminal antigens is thought to be a major perpetuating factor and a major cause of the “cytokine storm” through immune activation [3]. However, epithelial barrier function in A-GVHD may not only be relevant for the pathophysiology of immune activation but also for the pathomechanism of diarrhea in this disease. Therefore, we investigated the epithelial barrier function in human biopsies ex vivo in Ussing-type chambers with subsequent molecular characterization of potential pathomechanisms.

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Acknowledgements

We thank the team of the endoscopy unit (Campus Benjamin Franklin, Charité .- Universitätsmedizin Berlin) for the excellent cooperation and in memoriam D. Sorgenfrei for his remarkable technical assistance in the lab. This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG): Schu 559/11-2

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Authors and Affiliations

  1. Department of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Hanno Troeger, Christian Bojarski & Britta Siegmund

  2. Department of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Nina A. Hering

  3. Institute of Clinical Physiology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

    Anja Fromm, Christian Barmeyer, Michael Fromm & Jörg-Dieter Schulzke

  4. Department of Hematology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Lutz Uharek & Kathrin Rieger

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  1. Hanno Troeger
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Correspondence to Jörg-Dieter Schulzke.

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These authors contributed equally: Kathrin Rieger, Jörg-Dieter Schulzke

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Troeger, H., Hering, N.A., Bojarski, C. et al. Epithelial barrier dysfunction as permissive pathomechanism in human intestinal graft-versus-host disease. Bone Marrow Transplant 53, 1083–1086 (2018). https://doi.org/10.1038/s41409-018-0144-2

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