Gene expression data from human intestinal biopsies

Anti-TNFα therapy induces mucosal healing in a large proportion of Crohn’s disease (CD) patients, but the mechanisms underlying this process are not fully elucidated. To this end we examined molecular effects of adalimumab treatment in CD. CD patients (n=10) underwent ileocolonoscopy were sampled for mucosal biopsies before and after three months of adalimumab treatment. Collected material was analyzed using transcriptome microarray analysis. All patients were responders and eight patients reached clinical remission. Mucosal transcriptome analyses demonstrated that anti-inflammatory and tissue-repair gene-sets were upregulated in inflamed mucosa, in addition to proinflammatory and tissue-destruction-related genes. After treatment, genes promoting inflammation or tissue-destruction were downregulated. , and these genes are primarily expressed in innate leukocytes and stromal cells. Expression of anti-inflammatory and tissue-repair-related genes was also downregulated, but to a lesser degree. Of note, various parts of the colon displayed distinct gene-expression profiles. Adalimumab operates by down-shifting several proinflammatory arms of both the innate and adaptive immune-system, but does not disturb regulatory T-cells. Anti-inflammatory and tissue-repair machineries are upregulated already during active inflammation, but are not effective until proinflammatory drivers have been silenced. 76 intestinal samples from 10 patients were analyzed. 4 samples had a second replicates.