title: Alterations in mucosal immunity identified in the colon of patients with irritable bowel syndrome.
abstract: OBJECTIVE
  Irritable bowel syndrome (IBS) has been associated with mucosal dysfunction, mild inflammation, and altered colonic bacteria. We used microarray expression profiling of sigmoid colon mucosa to assess whether there are stably expressed sets of genes that suggest there are objective molecular biomarkers associated with IBS.
  
  
  METHODS
  Gene expression profiling was performed using Human Genome U133 Plus 2.0 (Affymetrix) GeneChips with RNA from sigmoid colon mucosal biopsy specimens from 36 IBS patients and 25 healthy control subjects. Real-time quantitative polymerase chain reaction was used to confirm the data in 12 genes of interest. Statistical methods for microarray data were applied to search for differentially expressed genes, and to assess the stability of molecular signatures in IBS patients.
  
  
  RESULTS
  Mucosal gene expression profiles were consistent across different sites within the sigmoid colon and were stable on repeat biopsy over approximately 3 months. Differentially expressed genes suggest functional alterations of several components of the host mucosal immune response to microbial pathogens. The most strikingly increased expression involved a yet uncharacterized gene, DKFZP564O0823. Identified specific genes suggest the hypothesis that molecular signatures may enable distinction of a subset of IBS patients from healthy controls. By using 75% of the biopsy specimens as a validation set to develop a gene profile, the test set (25%) was predicted correctly with approximately 70% accuracy.
  
  
  CONCLUSIONS
  Mucosal gene expression analysis shows there are relatively stable alterations in colonic mucosal immunity in IBS. These molecular alterations provide the basis to test the hypothesis that objective biomarkers may be identified in IBS and enhance understanding of the disease.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, Division of Janssen Pharmaceutica n.v., Beerse, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Aerssens
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Willem
authors.initials: W
authors.lastname: Talloen
authors.forename: Leen
authors.initials: L
authors.lastname: Thielemans
authors.forename: Hinrich W H
authors.initials: HW
authors.lastname: Göhlmann
authors.forename: Ilse
authors.initials: I
authors.lastname: Van Den Wyngaert
authors.forename: Theo
authors.initials: T
authors.lastname: Thielemans
authors.forename: Ronald
authors.initials: R
authors.lastname: De Hoogt
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Andrews
authors.forename: Adil E
authors.initials: AE
authors.lastname: Bharucha
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Carlson
authors.forename: Irene
authors.initials: I
authors.lastname: Busciglio
authors.forename: Duane D
authors.initials: DD
authors.lastname: Burton
authors.forename: Thomas
authors.initials: T
authors.lastname: Smyrk
authors.forename: Raul
authors.initials: R
authors.lastname: Urrutia
authors.forename: Bernard
authors.initials: B
authors.lastname: Coulie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003106:Colon / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology*; D043183:Irritable Bowel Syndrome / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D012333:RNA, Messenger; D012313:RNA