Published ahead of print on September 4, 2003, doi:10.1164/rccm.200305-644OC
Am. J. Respir. Crit. Care Med., Volume 168, Number 10, November 2003, 1237-1242
A more recent version of this article appeared on November 15, 2003
Submitted on May 23, 2003
Accepted on September 1, 2003
Gene Expression Profiling of Bronchoalveolar Lavage Cells in Acute Lung Rejection
Vincent J Gimino1, Jeffrey D Lande2, Todd R Berryman2, Richard A King3, and Marshall I Hertz1*
1 Medicine, University of Minnesota, Minneapolis, MN, USA,
2 Genetics, University of Minnesota, Minneapolis, MN, USA; Medicine, University of Minnesota, Minneapolis, MN, USA,
3 Genetics, University of Minnesota, Minneapolis, MN, USA
* To whom correspondence should be addressed. E-mail: hertz001{at}umn.edu.
Lung transplantation is effective for many diseases unresponsive to other therapy. However, long-term survival of recipients is limited by the development of bronchiolitis obliterans syndrome. There are no reliable biomarkers of acute rejection, although it is common, and is the leading risk factor for the bronchiolits obliterans syndrome. Gene expression microarrays were performed using bronchoalveolar lavage cells of lung transplant recipients with acute rejection (n=27) and with no rejection (n=7). The cell counts and differential counts were similar. Signal values between groups were compared with T-tests. 135 genes were up-regulated in the acute rejection group including genes known to be involved in the acute rejection response, immune response genes with an unknown role in rejection, non-immunologic genes with an unknown role in rejection, and genes of unknown function. 2D hierarchical clustering grouped all acute rejection samples, and the majority of the no rejection samples. The acute rejection samples showed significant changes in gene expression for 7 biological pathways. Bronchoalveolar lavage cells are a reliable RNA source for microarray analysis, which is powerful in identifying genes involved in acute rejection. The individual genes, patterns of gene expression, or biologic pathways identified may represent novel biomarkers for acute rejection.
Key words: lung transplantation, gene expression, acute rejection, microarray.
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