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Clinical and Developmental Immunology
Volume 13 (2006), Issue 2-4, Pages 265-271

Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes

1Division of Gastroenterology, University of California, Davis, PSSB #3500, 4150 V Street, Sacramento 95817, CA, USA
2Molecular and Cell Biology, NIH National Center of Excellence Nutritional Genomics, University of California, Davis 95616, CA, USA
3Division of Rheumatology, Allergy and Clinical Immunology, 451 East Health Sciences Drive, GBSF 6510, Davis 95616, CA, USA

Copyright © 2006 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Primary sclerosing cholangitis (PSC) is a chronic disease of the bile ducts characterized by an inflammatory infiltrate and obliterative fibrosis. The precise role of the immune system in the pathogenesis of PSC remains unknown. We used RNA microarray analysis to identify immune-related genes and pathways that are differentially expressed in PSC. Messenger RNA (mRNA) from peripheral blood mononuclear cells (PBMC) was isolated from both patients with PSC and age and sex matched healthy controls. Samples from 5 PSC patients and 5 controls were analyzed by microarray and based upon rigorous statistical analysis of the data, relevant genes were chosen for confirmation by RT-PCR in 10 PSC patients and 10 controls. Using unsupervised hierarchical clustering, gene expression in PSC was statistically different from our control population. Interestingly, genes within the IL-2 receptor beta, IL-6 and MAP Kinase pathways were found to be differently expressed in patients with PSC compared to controls. Further, individual genes, TNF-α induced protein 6 (TNFaip6) and membrane-spanning 4-domains, subfamily A (ms4a) were found to be upregulated in PSC while similar to Mothers against decapentaplegic homolog 5 (SMAD 5) was downregulated. In conclusion, several immune-related pathways and genes were differentially expressed in PSC compared to control patients, giving further evidence that this disease is systemic and immune-mediated.