Bronchial epithelial cells as a new source for differential transcriptome analysis after lung transplantation

Objective: The early diagnosis of chronic organ rejection after lung transplantation (LTx) is currently hampered by the lack of reliable diagnostic markers. The present study aims to establish the procedure of gene expression profiting in bronchial epithelial. cells for the identification of candidate genes that might prove useful in the early diagnosis. Methods: Twenty-three patients who underwent lung transplantations were investigated at a time point when no clinical signs of bronchiolitis obliterans syndrome (BOS) were apparent. Bronchial epithelial cells were obtained by bronchial brushing. Gene expression profiles were determined using a human whole-genome cDNA microarray (Stanford Faculty, Stanford, CA, USA). Results: Unsupervised hierarchical cluster analysis revealed that the samples from LTx patients can be clearly distinguished from the comparison group. We also found that the samples from LTx patients with the same underlying disease do not form major clusters of gene expression pattern. Using biostatistical analysis, 'haemoglobin beta', expressed by alveolar type II and Clara cells, and CD99, involved in inflammatory processes, were identified comparing lung transplantation and comparison group. Conclusions: Thus, global expression analyses of bronchial epithelial cells might be a new approach to identify diagnostic markers, especially if patients with LTx are monitored sequentially and if patients with and without BOS are compared.