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Gene Expression Profiling of Bronchoalveolar Lavage Cells in Acute Lung Rejection

Department of Medicine and Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota

Correspondence and requests for reprints should be addressed to Marshall I. Hertz, M.D., University of Minnesota, 420 Delaware St. SE, MMC 276, Minneapolis, MN 55405. E-mail: hertz001{at}umn.edu

Lung transplantation is effective for many diseases that are unresponsive to other therapy. However, long-term survival of recipients is limited by the development of bronchiolitis obliterans syndrome. Acute rejection is a major risk factor for bronchiolitis obliterans syndrome, but noninvasive biomarkers have not been identified. To address this deficiency, gene expression microarrays were performed using bronchoalveolar lavage cells of lung transplant recipients with acute rejection (n = 7) and with no rejection (n = 27). The cell and differential counts were similar. Signal values for genes between groups were compared using t tests. One hundred thirty-five genes were upregulated in the acute-rejection group, including genes involved in acute rejection, immune response genes with an unknown role in rejection, genes not known to have a role in rejection, and genes of unknown function. Two-dimensional hierarchical clustering grouped all acute rejection samples into one cluster and the majority of the no-rejection samples into a second cluster. The acute-rejection samples showed significant changes in gene expression for seven biological pathways. Bronchoalveolar lavage cells are a reliable RNA source for microarray analysis, which is powerful in identifying acute-rejection genes. The individual genes, patterns of gene expression, or biologic pathways identified may represent novel biomarkers for acute rejection.

Key Words: lung transplantation • allograft rejection • microarray

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