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English summary: Xenotransplantation and ABO-Incompatibility
The current organ shortage in transplantation medicine stimulates the exploration of new strategies to expand the donor pool including the utilization of living donors, ABO-incompatible grafts and xenotransplantation. Preformed natural antibodies (NAb) such as anti-A/B histoblood group isoagglutinins and xenoreactive anti-Galα1,3Gal antibodies mediate humoral graft rejection whereas delayed xenograft rejection (DXR) in xenotransplanatation is characterized by graft infiltration with innate immune cells. Monocytes and polymorphonuclear neutrophils (PMN) are among the earliest recruited to xenografts and NK cells play a much more significant role in the rejection of xenografts than allografts. Our research projects focus on the following goals:
- Study the molecular mechanisms of the early interactions between porcine endothelium and human leukocyte subsets, and to develop tools for the inhibition of such interactions in xenotransplantation. On the one hand we focus on adhesion and transmigration in collaboration with Pr. B. Imhof, on the other hand on NK cell-mediated endothelial cell damage.
- Analyse the immunologic mechanisms and clinical outcome associated with ABO-incompatible hematopoietic stem cell transplantation (HSCT) and SOT in collaboration with the Service of Hematology (Pr. J. Passweg), Nephrology (K. Hadaya) and the Dep of Surgery (Pr. L. Bühler). The immediate goals are to analyze the mechanisms leading to the spontaneous disappearance of anti-A/B antibodies following minor ABO-incompatible HSCT, a phenomenon of immunological tolerance; the occurrence of endothelial cell chimerism after HSCT; and the effects of pretransplant column immunoabsorption on total, anti-blood group A/B and anti-vaccine specific Ab levels prior to ABO-incompatible renal transplantation in order to improve future protocols.
- Reactivation of human cytomegalovirus (hCMV) is a potential risk following the clinical application of pig-to-human xenotransplantation. Since little is known about undesirable side-effects arising from hCMV infection of porcine organs, we investigate the molecular effects of human CMV infection in porcine and human endothelial cells, and the resulting influence on human leukocyte chemotaxis, adhesion, transmigration, and cellular effector functions.