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Altered STAT4 Isoform Expression in Patients with Inflammatory Bowel Disease.

ABSTRACT: Crohn's disease (CD) and ulcerative colitis (UC) are the major forms of inflammatory bowel disease, and pathogenesis involves a complex interplay among genetic, environmental, and immunological factors. We evaluated isoform expression of the IL-12-activated transcription factor STAT4 in children with CD and UC.We collected biopsy samples from both patients newly diagnosed with CD and with UC. We further collected blood samples from patients newly diagnosed with CD and with UC as well as from patients who had a flare-up after being in clinical remission, and we examined the ratios of STAT4?/STAT4? mRNA. In addition to STAT4 isoforms, we measured the expression of the cytokines TNF?, IFN?, granulocyte macrophage-colony stimulating factor, and IL-17 using polymerase chain reaction of biopsy samples and multiplex analysis of patient serum samples.Ratios of STAT4?/STAT4? were increased in specific gastrointestinal tract segments in both patients with CD and those with UC that correlate with the location and severity of inflammation. In contrast, we did not observe changes in STAT4?/STAT4? ratios in biopsy specimens from patients with eosinophilic esophagitis. We also observed increased STAT4?/STAT4? ratios in the peripheral blood mononuclear cells of patients with UC and those with CD, compared with healthy controls. Ratios were normalized after patients were treated with steroids.Collectively, these data indicate that STAT4 isoforms could be an important noninvasive biomarker in the diagnosis and treatment of inflammatory bowel disease and that expression of these isoforms might provide further insight into the pathogenesis of IBD.

SUBMITTER: Jabeen R

PROVIDER: S-EPMC4567388 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Altered STAT4 Isoform Expression in Patients with Inflammatory Bowel Disease.

Jabeen Rukhsana R Miller Lucy L Yao Weiguo W Gupta Sandeep S Steiner Steven S Kaplan Mark H MH

Inflammatory bowel diseases 20151001 10

<h4>Background</h4>Crohn's disease (CD) and ulcerative colitis (UC) are the major forms of inflammatory bowel disease, and pathogenesis involves a complex interplay among genetic, environmental, and immunological factors. We evaluated isoform expression of the IL-12-activated transcription factor STAT4 in children with CD and UC.<h4>Methods</h4>We collected biopsy samples from both patients newly diagnosed with CD and with UC. We further collected blood samples from patients newly diagnosed with ...[more]

PMID: 26177303

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Project description:Notwithstanding uncertain pathogenesis of inflammatory bowel disease (IBD), deregulation of adaptive immunity is paramount for the development of inflammation. Essential role in the resolution of inflammation is played by apoptosis, deregulated in lymphocytes isolated from inflamed intestine. Despite IBD being a systemic disease, little is known about apoptosis of peripheral lymphocytes. The concentrations of Bcl-2, cytochrome c, p53, and caspase-9 were determined (ELISA) in lymphocyte-enriched fractions of peripheral blood mononuclear cells (LE-PBMCs) from 64 individuals (42 with IBD) and related to IBD phenotype and activity, treatment, and inflammatory and hematological indices. The diagnostic potential of evaluated markers was determined as well. All evaluated molecules were significantly lower in IBD patients, of which cytochrome c and p53 were significantly lower exclusively in patients with Crohn's disease (CD) and cytochrome c differed significantly between CD and ulcerative colitis (UC). Caspase 9 was significantly lower in active IBD and Bcl-2 in active UC whereas cytochrome c was higher in active CD. Treatment with corticosteroids affected the concentrations of cytochrome c and p53. Both positively correlated with hsCRP and the concentrations of all markers were interrelated. As IBD markers, Bcl-2 and caspase-9 displayed good accuracy and, as a panel of markers with cytochrome c, their accuracy was excellent (92%). As CD markers Bcl-2, cytochrome c, and p53 displayed fair accuracy but combined determination of Bcl-2 and cytochrome c improved the accuracy to 85%. Taken together, our results imply diminished intrinsic apoptotic capacity of LE-PBMCs in IBD but an upregulation of proapoptotic features parallel to increasing severity of inflammation. Observed abnormalities in intrinsic pathway of apoptosis are more pronounced in CD. Upon positive validation on a larger set of patients, combined quantification of Bcl-2 and cytochrome c might be considered as an adjunct in differential diagnosis of UC and CD of colon and rectum.

Dataset Information

Altered STAT4 Isoform Expression in Patients with Inflammatory Bowel Disease.

Publications

Altered STAT4 Isoform Expression in Patients with Inflammatory Bowel Disease.

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