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JMD 2006, Vol. 8, No. 1
Copyright © 2006 American Society for Investigative Pathology & Association for Molecular Pathology

Molecular Classification of Crohn’s Disease and Ulcerative Colitis Patients Using Transcriptional Profiles in Peripheral Blood Mononuclear Cells

Michael E. Burczynski^*, Ron L. Peterson, Natalie C. Twine, Krystyna A. Zuberek, Brendan J. Brodeur, Lori Casciotti, Vasu Maganti, Padma S. Reddy, Andrew Strahs^¶, Fred Immermann^||, Walter Spinelli^**, Ulrich Schwertschlag, Anna M. Slager^*, Monette M. Cotreau and Andrew J. Dorner

From the Molecular Profiling and Biomarker Discovery/Biomarker Laboratory * and Clinical Research and Development, ** Wyeth Research, Collegeville, Pennsylvania; Molecular Profiling and Biomarker Discovery, Inflammation Research, Bioinformatics Client Services, Clinical Statistics, ^¶ and Translational Research, Wyeth Research, Cambridge, Massachusetts; and Biometrics Research, ^|| Wyeth Research, Pearl River, New York

Ulcerative colitis (UC) and Crohn’s disease (CD) are common inflammatory bowel diseases producing intestinal inflammation and tissue damage. Although emerging evidence suggests these diseases are distinct, 10% of patients remain classified as indeterminate inflammatory bowel disease even after invasive colonoscopy intended for diagnosis. A molecular diagnostic assay using a clinically accessible tissue would greatly assist in the classification of these diseases. In the present study we assessed transcriptional profiles in peripheral blood mononuclear cells from 42 healthy individuals, 59 CD patients, and 26 UC patients by hybridization to microarrays interrogating more than 22,000 sequences. Supervised analysis identified a set of 12 genes that distinguished UC and CD patient samples with high accuracy. The alterations in transcript levels observed by microarray were verified by real-time polymerase chain reaction. The results suggest that a peripheral blood mononuclear cell-based gene expression signature can provide a molecular biomarker that can complement the standard dia-gnosis of UC and CD.

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