Cell-free DNA and immune cell dynamics in acute graft-versus-host disease and systemic inflammation

Acute graft-versus-host disease (aGvHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Affecting 30-50% of allo-HSCT recipients, aGvHD limits the broader use of this treatment. The pathogenesis of aGvHD is complex, involving donor immune cells attacking recipient tissues in the context of systemic inflammation. However, predicting the onset and severity of aGvHD remains a challenge, and ongoing efforts focus on identifying reliable biomarkers and refining biomarker panels. The work in this thesis explores the role of cell-free DNA (cfDNA) as a potential biomarker for aGvHD. We show that cell-free DNA (cfDNA) is increased in systemic inflammation, sepsis, and around the onset of aGvHD. We propose that cfDNA initially originates from a hematopoietic source followed by the release from damaged parenchymal tissue. By determining both the quantity and origin of cfDNA, we aim to enhance the prediction of aGvHD and evaluation of treatment efficacy in aGvHD. The second part of this thesis focuses on immune cell profiling in the context of aGvHD using multi-panel flow cytometry. We identify immune cell subsets that correlate with aGvHD in a small cohort of allo-HSCT patients, providing promising insights, though further investigation is warranted. Focusing on innate lymphoid cells (ILC), our work suggests that grafts rich in ILC, particularly ILC3, are significantly correlated to a reduced risk of aGvHD development. The use of adoptive transfer of ILC is an interesting treatment of aGvHD prevention to explore in the future.