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Project

The allogeneic immune response in chronic rejection after lung transplantation – A study of human and mouse

Lung transplantation is a well-accepted treatment option for patients with end-stage lung disease. The outcome of lung transplantation is hampered by chronic rejection, which has a  50% prevalence 5years after transplantation. Due to chronic rejection the mortality rate in lung transplantation (50% after 5 years) is much higher compared to other solid organ transplantations (<30% after 5 years). Until recently, the treatment of chronic rejection was insufficient and could only stop the decline in lung function in some patients.

With the introduction of the neo-macrolide azithromycin, up to 40% of the patients with proven chronic rejection have shown improvement of lung function and some even completely recovered. Thanks to this new treatment the prevalence of chronic 2 years after lung transplantation in our center diminished from 30% (comparable to data from the international society of heart and lung transplantation) to 15%.

The mechanism of chronic rejection is driven by both immunologic (eg. acute rejection, lymphocytic bronchiolitis) and non-immunologic factors (reflux, airway colonization, air pollution), however it is not yet completely understood and is the focus of this project.

The experimental approach of this PhD project is twofold, starting on the one hand with an easy trachea transplant model where tracheal obliteration is present at day 28 post transplant, allowing us to generate rapidly output. And on the second hand, work with a complex mouse orthotopic left lung transplant model where chronic rejection lesions are observed after 10 weeks.

The current project will explore the role of cellular and humoral immunity in chronic rejection after lung transplantation, and potential treatment option. A first target will be on T and B cells by applying immunostaining and immunoglobuline protein determinations (by ELISA, multiplex CBA). The second aim is to investigate how the structural changes to the lung are evolving over time by histology, immunostaining and microCT and how they relate to the human situation. And finally treatment options to explore are azithromycin, pirfenidone, vitamin D and extracorporeal photopheresis (ECP).

Date:1 Dec 2015 →  6 Nov 2023
Keywords:Lung Transplantation, Adaptive Immunsystem, Chronic Rejection
Disciplines:Respiratory medicine
Project type:PhD project