cDNA microarray analysis of gene expression in coeliac disease jejunal biopsy samples.
In coeliac disease in the jejunum of a genetically susceptible person wheat gliadin and related prolamins from rye and barley trigger an immunological reaction, which induces small-bowel mucosal transformations, villous atrophy and crypt hyperplasia. Though CD4+ specific T cells, intraepithelial lymphocytes, infiltrating plasma cells and autoantibodies are known to have an effect on the coeliac disease, the pathogenic mechanisms leading to the tissue injury remain to be elucidated. Our aim was to find novel gene transcripts, which might have a role in coeliac disease pathogenesis. The gene expression in duodenal biopsy samples from untreated coeliac patients (n=4), patients on gluten-free diet (n=4) and healthy controls (n=4) was studied by cDNA microarray analysis. The method allows monitoring of the expression of thousands of genes simultaneously. Compared to healthy controls, the expression of 156 and 60 genes was changed in untreated and treated coeliac disease, respectively. Between treated and untreated coeliac disease, 98 genes had altered expression. Of the 5184 genes or expressed sequence tags, altogether 263 were affected. Many of these genes are directly or indirectly connected to T-cell activation, B-cell maturation or epithelial cell differentiation. By the microarray method, numerous genes were found to evince altered mRNA expression in coeliac disease. The method holds promise in exploring the pathogenetic mechanisms in the small bowel and may reveal new target genes for the therapy of coeliac disease.
Juuti-Uusitalo
K
K
Paediatric Research Centre, Tampere University Hospital, University of Tampere, FIN-33014 Tampere, Finland. lokaju@uta.fi
Mäki
M
M
Kaukinen
K
K
Collin
P
P
Visakorpi
T
T
Vihinen
M
M
Kainulainen
H
H
D000328:Adult; D000368:Aged; D001706:Biopsy; D002446:Celiac Disease / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007583:Jejunum / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction