Pathophysiology of gastrointestinal acute graft-versus-host disease and the potential role of glucagon-like peptide 2 |
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| Authors: | Robert Zeiser Yi-Bin Chen Nader N. Youssef Francis Ayuk |
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| Affiliation: | 1. Faculty of Medicine, Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Medical Center—University of Freiburg, Freiburg, Germany;2. Hematopoietic Cell Transplant and Cell Therapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA;3. VectivBio AG, Basel, Switzerland;4. Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany |
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| Abstract: | Acute graft-versus-host disease (aGVHD) is a life-threatening complication after allogeneic haematopoietic cell transplantation, with gastrointestinal (GI) tract involvement (GI aGVHD) being one of the leading causes of morbidity and mortality. Whilst systemic steroids are the standard first-line treatment for aGVHD, approximately 50% of patients become steroid refractory (SR), which is associated with poor outcomes. Existing options for SR-GVHD are limited, and there is a significant unmet need for new non-immunosuppressive treatment approaches in patients with GI aGVHD. Here, we review newer concepts in the pathogenesis of GI aGVHD and present the evidence for the role of glucagon-like peptide 2 (GLP-2) in maintaining and protecting GI epithelial cells, including the enterocytes, intestinal stem cells and Paneth cells, which are direct targets of aGVHD. Finally, we discuss the therapeutic rationale for GLP-2 treatment as a tissue regeneration approach and the potential use of the novel GLP-2 analogue apraglutide as an adjunctive treatment for GI aGVHD. |
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| Keywords: | GVHD HSC transplantation transplant |
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