Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes
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 pa...
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| Format: | Article |
| Language: | English |
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Wiley
2006-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1080/17402520600800085 |
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| author | Christopher A. Aoki Kevin Dawson Thomas P. Kenny M. Eric Gershwin Christopher L. Bowlus |
| author_facet | Christopher A. Aoki Kevin Dawson Thomas P. Kenny M. Eric Gershwin Christopher L. Bowlus |
| author_sort | Christopher A. Aoki |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-37c8736435fb43ba9148213fa4357f1e |
| institution | DOAJ |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2006-01-01 |
| publisher | Wiley |
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| series | Clinical and Developmental Immunology |
| spelling | doaj-art-37c8736435fb43ba9148213fa4357f1e2025-08-20T03:20:29ZengWileyClinical and Developmental Immunology1740-25221740-25302006-01-01132-426527110.1080/17402520600800085Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated GenesChristopher A. Aoki0Kevin Dawson1Thomas P. Kenny2M. Eric Gershwin3Christopher L. Bowlus4Division of Gastroenterology, University of California, Davis, PSSB #3500, 4150 V Street, Sacramento 95817, CA, USAMolecular and Cell Biology, NIH National Center of Excellence Nutritional Genomics, University of California, Davis 95616, CA, USADivision of Rheumatology, Allergy and Clinical Immunology, 451 East Health Sciences Drive, GBSF 6510, Davis 95616, CA, USADivision of Rheumatology, Allergy and Clinical Immunology, 451 East Health Sciences Drive, GBSF 6510, Davis 95616, CA, USADivision of Gastroenterology, University of California, Davis, PSSB #3500, 4150 V Street, Sacramento 95817, CA, USAPrimary 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.http://dx.doi.org/10.1080/17402520600800085 |
| spellingShingle | Christopher A. Aoki Kevin Dawson Thomas P. Kenny M. Eric Gershwin Christopher L. Bowlus Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes Clinical and Developmental Immunology |
| title | Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes |
| title_full | Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes |
| title_fullStr | Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes |
| title_full_unstemmed | Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes |
| title_short | Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes |
| title_sort | gene expression by pbmc in primary sclerosing cholangitis evidence for dysregulation of immune mediated genes |
| url | http://dx.doi.org/10.1080/17402520600800085 |
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