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Project

The role of the B-cell mediated immunuunrespons in phenotypes of chronic rejection after lung transplantation.

B-cells are important players in the adaptive immune system. Their principal functions are to make antibodies against antigens, to perform the role of antigen-presenting cells (APCs), and to develop into memory B cells after activation by antigen interaction. B-cells have been shown to play an important role in chronic respiraotry diseases like COPD and IPF. With this research, we want to establish a role for B-cells in chronic lung allograft dysfunction (CLAD), with special attention towards the clinical phenotype of CLAD being Bronchiolitis Obliterans Syndrome (BOS) versus Restrictive Allograft Syndrome (RAS). We want to investigate the role of B-cells and antibodies in early and late disease and confirm our findings in a mouse model.To establish a role for B-cells, we will use human BAL, blood and tissue samples wherein we will investigate the presence of B-cells (immunohistochemistry and gene expression analysis on explanted lung specimens) and antibodies (immunoglobulins in BAL and anti-HLA antibodies in serum), but also a mouse model of heterotopic trachea transplantation to consolidate our findings. Lastly, we will use the mousemodel to assess the potential of pirfenidone and extracorporeal photopheresis to attenuate disease. We believe that this research will improve the understanding of the mechanism of CLAD and might be valuable for further therapeutic treatment of CLAD.

Date:1 Jan 2016 →  31 Dec 2018
Keywords:long transplantatie, chronische afstoting, fenotypes, immunuunrespons, B-cell gemedieerde
Disciplines:Immunology