Balance between herpes viruses and immunosuppression after lung transplantation

This thesis focuses on the interplay between two Herpes Virus infections and the immunosuppression used after solid organ (and especially lung) transplantation. It starts with the description of diagnostic tools of Cytomegalovirus (CMV) and their therapeutic implications. Then it addresses the major clinical complication of a second herpes virus, the Epstein-Barr virus (EBV), namely Post Transplant Lymphoproliferative Disease (PTLD). These chapters describe the work done to come to a diagnostic tool to predict patients at risk for PTLD and they discuss clinical presentation and treatment of PTLD. We come to the new conclusion that EBV is associated with transplant dysfunction. We subsequently implemented a pre-emptive strategy for PTLD in our lung transplant program, and the results are shown in chapter 11 and 12. Finally, we propose that EBV DNA load can be used as a surrogate marker for over-immunosuppression after lung (and probably also other solid organ) transplantation, and, thus may help to guide and individualize immunosuppression. This summary contains two parts: the first part introduces the different chapters and describes their most important results, the second part summarizes the conclusions and speculates on the clinical implications and future perspective/research

The cellular composition of the lung lining fluid gradually changes from bronchus to alveolus

Although large advances have recently been made mapping out the cellular composition of lung tissue using single cell sequencing, the composition and distribution of the cellular elements within the lining fluid of the lung has not been extensively studied. Here, we assessed the cellular composition of the lung lining fluid by performing a differential cell analysis on bronchoalveolar lavage fluid (BALF) and epithelial lining fluid (ELF) at four different locations within the lung in post-lung transplantation patients. The percentage of neutrophils and lymphocytes is reduced in more distal regions of the lungs, while the percentage of macrophages increases in these more distal regions. These data provide valuable information to determine which lung lining fluid sampling technique and location is best to use for measuring specific factors and biomarkers, and to increase the understanding of different cell populations in specific lung regions