Clinical and immunological aspects of pretransplant blood transfusions

Waanders, M.M. (2009)

Doctoral Thesis

Blood transfusions can lead to immunization or tolerance in the recipient. The latter is characterized by an improved transplant outcome after pretransplant blood transfusions. First observations of improved kidney graft outcome after blood transfusion date 35 years back, however no exclusive immunological mechanism has been found yet. At the Leiden University Medical Center, patients on the waiting list for simultaneous pancreas-kidney transplantation (SPKT) received a non-leukocyte depleted, HLA-DR shared blood transfusion before transplantation. We showed that a pretransplant blood transfusion was able to diminish the severity of acute rejection episodes after SPKT. The need for HLA-DR sharing suggests a role for the indirect allorecognition. Our in vitro experiments focusing on the indirect allorecognition and on several subsets of recipient immune cells, showed that a pretransplant blood transfusion activates the recipient__s immune system. It is still not clear if and how this activation state can lead to transplantation tolerance. Additionally, there may be a role for microchimeric donor cells in the immunological mechanism leading to tolerance. Pretransplant blood transfusions may still be of clinical benefit in these times of potent immunosuppressive drug use, but requires the support of well-designed RCTs as well as more insight into the immunological mechanism.

• Blood transfusion
• HLA-DR
• Immune modulation
• Indirect allorecognition
• Pretransplant
• Regulatory T cells
• Transplantation

• All authors: Waanders, M.M.
• Supervisor: Claas, F.H.J.; Brand, A.
• Co-supervisor: Roelen, D.L.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2009-09-22
• ISBN (print): 9789090244617
• Sponsorship: Sanquin, Corning, BD Biosciences, Stichting NRC, Wyeth, Clean Air Techniek, Greiner, Novartis