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(Chest. 2006;130:847-854.)
© 2006 American College of Chest Physicians

Sequential Gene Expression Profiling in Lung Transplant Recipients With Chronic Rejection*

Brandon S. Lu, MD; Andrew D. Yu, MD; Xiaofeng Zhu, MD; Edward R. Garrity, Jr, MD, FCCP; Wickii T. Vigneswaran, MD, FCCP and Sangeeta M. Bhorade, MD, FCCP

* From the Department of Neurology (Dr. Lu), Northwestern University, Feinberg School of Medicine, Chicago, IL; the Department of Pulmonary, Critical Care, and Sleep Medicine (Dr. Yu), DuPage Medical Group, Lombard, IL; the Department of Preventive Medicine and Epidemiology (Dr. Zhu), Loyola University Medical Center, Maywood, IL; the Department of Medicine (Drs. Garrity and Bhorade), Section of Pulmonary and Critical Care, and the Department of Cardiac and Thoracic Surgery (Dr. Vigneswaran), University of Chicago, Chicago, IL.

Correspondence to: Sangeeta M. Bhorade, MD, FCCP, University of Chicago Hospitals, 5841 S Maryland Ave, MC 6076, Chicago, IL 60637; e-mail: sbhorade{at}medicine.bsd.uchicago.edu

Abstract

Study objectives: Chronic allograft rejection is the leading cause of morbidity and mortality for long-term survivors of lung transplantation. Previous studies have implicated only isolated genes in the development of chronic rejection and have not examined multiple pathways in an individual concurrently. Using microarray technology, we identified and compared gene expression profiling in lung transplant recipients with and without chronic rejection, and follow sequential expression of genes differentially expressed between the two groups.

Design: Prospective, cohort study.

Setting: Single lung transplant center.

Patients or participants: Eleven transplant recipients with chronic rejection were matched with 9 control transplant recipients.

Interventions: All recipients underwent surveillance bronchoscopies at predetermined times to rule out infection and/or acute rejection. Gene expression profiling was obtained from hybridizing BAL fluid cell RNA to a 96-gene microarray.

Measurements and results: Fifteen genes were found to be significantly differentially expressed between the two patient groups, and they are involved in inflammatory, fibrotic, and apoptotic pathways. Temporal expression of the significant genes demonstrated a change in their levels at the onset of chronic rejection, with normalization to prerejection levels as rejection continued.

Conclusions: We conclude that microarray technology is valuable in studying the mechanism of chronic lung rejection, and the expression of genes in multiple pathways is elevated in patients with chronic lung rejection.

Key Words: BAL • graft rejection • lung transplantation • microarray analysis






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