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Immune cell composition and function in patients with and without steroid-refractory acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation
- Abstract
- One of the most serious life-threatening complications of allogeneic hematopoietic stem cell transplantation (allo-HCT) is acute and chronic graft-versus-host disease (GVHD). (1,2) The established first-line therapy of acute GVHD is methylprednisolone with an initial dose of 2 mg/kg body weight per day. But, only half of all patients respond to first-line therapy and the so-called steroid-refractory GVHD (SR-GVHD) is associated with a poor long-term prognosis. There is still an urgent need for biomarkers that predict response to glucocorticoid therapy. In a retrospective study we showed that cellular infiltrates of immune cells, like innate lymphoid cells (ILCs) and tissue-resident memory T cells (TRMs), differ at onset of gastrointestinal (GI) GVHD in patients who subsequently respond to glucocorticoid therapy compared to patients developing steroid-refractory disease. Based on these preliminary data, we hypothesize that GVHD affects the composition of immune cell populations in affected tissues, such as skin and GI tract, and cellular and molecular profiles of immune cells from peripheral blood (PB) and tissue biopsies, as well as the GI microbiome, may predict lack of response to glucocorticoid therapy. Furthermore, these cellular and molecular profiles may be prognostic for immune reconstitution after allo-HCT. Therefore, the aim of this study is to identify cellular and molecular profiles of GVHD in patients.
For this purpose, we will prospectively collect clinical data of patients undergoing allo-HCT at the Clinical Division of Hematology at the Medical University/University Hospital Graz, to create a database and compare patient’s clinical course with immune cell composition as well as function/activation state of the PB determined by flow cytometry and cytokine production, as we GI microbiome analysis and tissue samples (skin and GI) obtained from routine clinical biopsies using immunofluorescence, immunohistochemistry and High-Definition Spatial Transcriptomics (HDST). Results of blood and tissue immune cell analyses, cytokines and data from GI microbiome will be compared to the cli nical data on occurrence and severity of GVHD, response to GVHD therapy and patient outcome.
- Keywords
- Allogene Stammzelltransplantation
- GVHD
- Spender-gegen-Empfänger Erkrankung
- Steroidrefraktäre GVHD
- Project Leader:
- Gaksch Lukas
- Duration:
- 01.01.2024-31.12.2025
- Type of Research
- basic research
- Staff
- Gaksch, Lukas, Project Leader
- Pansy, Katrin, Co-worker
- Haingartner, Sandra, Co-worker
- Deutsch, Alexander, Co-worker
- MUG Research Units
- Division of Haematology