Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: insights into distinctive pathogenesis.
BACKGROUND
Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD) with variable, overlapping clinical features and complex pathophysiologies.


METHODS
To identify pathogenic processes underlying these disease subtypes, we used single endoscopic pinch biopsies to elucidate patterns of gene expression in active and inactive areas of UC and CD and compared these to infectious colitis and healthy control samples.


RESULTS
Unsupervised classification of a total of 36 samples yielded promising separation between the affected IBD, unaffected IBD, non-IBD colitis, and normal control samples, suggesting each sample type had a distinctive gene expression pattern. Genes differentially expressed in the CD samples compared to in the controls were related to IFNgamma-inducible TH1 processes (IFITM1, IFITM3, STAT1, and STAT3) and antigen presentation (TAP1, PSME2, PSMB8). The most noticeable change in the UC samples was reduced expression of genes regulating biosynthesis, metabolism, and electrolyte transport (HNF4G, KLF5, AQP8, ATP2B1, and SLC16A). Twenty-five percent of genes down-regulated in the UC samples were also down-regulated in the infectious colitis samples. Unaffected biopsy samples of IBD patients also registered differences expression of genes compared to in the normal controls. Of these differentially expressed genes, only 2 were up-regulated, PSKH1, a regulator of mRNA processing, and PPID, a suppressor of apoptosis.


CONCLUSIONS
The study shows that the gene expression patterns of IBD, CD in particular, are quite different from those of infectious colitis, highlighting distinctive expression of genes and pathways in UC and CD.
Wu
Feng
F
Department of Medicine (Gastroenterology Division), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Dassopoulos
Themistocles
T
Cope
Leslie
L
Maitra
Anirban
A
Brant
Steven R
SR
Harris
Mary L
ML
Bayless
Theodore M
TM
Parmigiani
Giovanni
G
Chakravarti
Shukti
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016000:Cluster Analysis; D003092:Colitis / Q000235:genetics / Q000473:pathology; D003093:Colitis, Ulcerative / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D003424:Crohn Disease / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004724:Endoscopy; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D007420:Intestine, Large / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction