Alterations in mucosal immunity identified in the colon of patients with irritable bowel syndrome.
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.
Aerssens
Jeroen
J
Johnson & Johnson Pharmaceutical Research & Development, Division of Janssen Pharmaceutica n.v., Beerse, Belgium.
Camilleri
Michael
M
Talloen
Willem
W
Thielemans
Leen
L
Göhlmann
Hinrich W H
HW
Van Den Wyngaert
Ilse
I
Thielemans
Theo
T
De Hoogt
Ronald
R
Andrews
Christopher N
CN
Bharucha
Adil E
AE
Carlson
Paula J
PJ
Busciglio
Irene
I
Burton
Duane D
DD
Smyrk
Thomas
T
Urrutia
Raul
R
Coulie
Bernard
B
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
D012333:RNA, Messenger; D012313:RNA