- Dr. Henderikus G. Otten, Principal Investigator
- Dr. Ed A. van de Graaf, Co-Investigator
- Dr. Ken I. Welsh, Advisor
- Dr. Jules M. van den Bosch, Advisor
- Dr. Frits G.J. Gmelig Meyling, Advisor
- University Medical Centre Utrecht, Utrecht, The Netherlands
- Prediction of Chronic Rejection which is the Main Cause of Long-Term Mortality after Lung Transplantation
The bronchiolitis obliterans syndrome (BOS) occurring after lung transplantation (LTx) is the main cause of long-term morbidity and mortality after LTx. Although the detailed etiology and pathogenesis of BOS are not clear, it has become evident that both the humoral and the cellular allogeneic immune response against airway epithelial cells (AEC), contributes significantly to the pathogenesis of BOS. Recently, it was demonstrated that the presence of patient antibodies reacting with non-HLA antigens expressed on AEC may precede BOS development, suggesting that such non-HLA antigenic systems may play a role in chronic lung allograft rejection. These data are in line with results obtained in kidney transplantation, in which it was demonstrated that endothelial cell-reactive non-HLA antibodies can be found in sera of patients which have suffered from hyperacute or acute kidney allograft rejection. Patient antibodies reactive with non-HLA antigens are at present not recognized due to the lack of suitable routine screening procedures.
The main purpose of this study is to identify non-HLA target antigens on donor lungs recognized by patient antibodies. Identification of these antigens may provide a routine screening technique which can predict the occurrence of BOS, by monitoring the development of humoral or T cell immunity against these antigens. Target antigens expressed on AEC recognized by patient sera can be identified by SEREX (serological analysis of antigens by recombinant expression cloning); an immunoscreening technique which is an established method for defining immunogenic antigens in a variety of disorders including malignancies and autoimmunities. This technique allows a high-resolution and sensitive search for antibody responses against proteins expressed by donor AEC. After identification of the non-HLA antigens recognized, it will be analysed which antibody or concomitant T cell responses are predictive for BOS development. If so, this can be used to guide immunosuppressive therapy after LTx.