Gene expression by PBMC in primary sclerosing cholangitis: Evidence for dysregulation of immune mediated genes

Christopher A. Aoki, Kevin Dawson, Thomas P. Kenny, M. Eric Gershwin, Christopher Bowlus

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)265-271
Number of pages7
JournalClinical and Developmental Immunology
Volume13
Issue number2-4
DOIs
StatePublished - Jun 2006

Keywords

  • Membrane-spanning 4-domains subfamily A (ms4a)
  • Microarray
  • Similar to mothers against decapentaplegic homolog 5 (SMAD 5)
  • TNF-α induced protein 6 (TNFaip6)

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Developmental Biology

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