Extrakorporale Photopherese mit UVC-behandelten Leukozyten im Vergleich zu 8-MOP/UVA-behandelten Leukozyten zur Therapie der akuten graft-versus-host disease im Mausmodell

Extracorporeal photopheresis with UV-C treated leucocytes in comparison to 8-MOP/UV-A treated leucocytes for the treatment of acute graft-versus-host disease in mice

by Carla Marie Zwerenz
Doctoral thesis
Date of Examination:2022-03-02
Date of issue:2022-02-28
Advisor:Prof. Dr. Tobias Legler
Referee:Prof. Dr. Tobias Legler
Referee:Dr. Ivan Prof Bogeski
Persistent Address: http://dx.doi.org/10.53846/goediss-9084

 

 

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Abstract

English

Graft-versus-host disease (GvHD) is a complication after allogeneic hematopoietic stem cell transplantation and responsible for the high morbidity and mortality rate. Extracorporeal photopheresis (ECP) is a common second-line treatment. ECP consists of the collection, irradiation and retransfusion of the patient’s leucocytes inducing apoptosis in these cells. For the irradiation process there is commonly used 8-methoxypsoralen (8-MOP) as a photosensitizer and UV-A radiation. Using UV-C radiation which is higher in energy would make it possible to forgo the 8-MOP. Without the injection of 8-MOP there would be a lower risk for bacterial contamination of the blood product. Additionally, there would be less risk for allergic reactions and increased photosensitivity for the patient. Using flow cytometry, we analyzed the rate of apoptosis and proliferation in a leukocyte subpopulation after 8-MOP/UV-A and UV-C treatment. Further, we used a mouse model of acute GvHD to investigate the effects of UV-C treated leucocytes in vivo. The apoptosis and proliferation rate in leukocytes after UV-C treatment were comparable to those after 8-MOP/UV-A treatment. In the mouse model of acute GvHD we could not see a significant therapeutic effect of either ECP treatment in comparison to the control group. Nonetheless, the UV-C treatment group showed a slight tendency to a higher survival rate compared to the 8-MOP/UV-A treatment group. Overall, in vitro we could show a similar effect for UV-C treatment in comparison to 8-MOP/UV-A treatment. Considering the in vivo result, that ECP treatment with UV-C radiation did not worsen the clinical status and that conventional ECP showed therapeutic effects in a lot of patients, we concluded that the final therapeutic potential of the UV-C treatment should be investigated further in future studies.
Keywords: Extracorporeal Photopheresis; Graft-versus-Host Disease; UVC