Journal
INFLAMMATORY BOWEL DISEASES
Volume 17, Issue 1, Pages 171-178Publisher
OXFORD UNIV PRESS INC
DOI: 10.1002/ibd.21352
Keywords
human; T Lymphocytes; methylation; interferon; IBD
Categories
Funding
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK043211, R37DK043211, P01DK046763] Funding Source: NIH RePORTER
- NIDDK NIH HHS [P01 DK046763, R01 DK043211, R37 DK043211, R37 DK043211-21] Funding Source: Medline
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Background: High antibody reactivity toward microbial antigens in Crohn's disease (CD) patients is predictive of a more aggressive disease course. However, few ulcerative colitis (UC) patients exhibit serologic reactivity toward microbial antigens. Mucosal expression of IFN-gamma plays a pivotal role in inflammatory bowel disease (IBD) pathogenesis. Recent genome-wide association studies (GWAS) surprisingly link UC, but not CD, risk loci to IFNG. We recently demonstrated that mucosal T cells from IBD patients exhibit distinct patterns of IFNG methylation compared to controls. This study evaluated the relationship between IFNG methylation and serologic and clinical profiles in peripheral T cells from IBD patients. Methods: DNA from peripheral T cells of 163 IBD patients (91 CD and 64 UC) and 42 controls was analyzed for methylation of eight IFNG sites. Serum markers ASCA, OmpC, I2, CBir, and pANCA were measured by enzyme-linked immunosorbent assay (ELISA). IFN-gamma secretion was measured by ELISA. Results: IBD patients requiring surgery exhibited reduced IFNG methylation compared to nonsurgical patients (P < 0.02). Enhancement of IFN-gamma secretion (P < 0.003), along with high antibody responses toward multiple microbial antigens (P < 0.017) in UC, but not CD, patients was correlated with decreased IFNG methylation. pANCA levels were not correlated with IFNG methylation. Conclusions: Levels of IFNG methylation were correlated with immune response to microbial components and expression of IFN-gamma in UC patients. Serological and epigenetic markers identify a subset of UC patients with an expression profile of a key TH1 pathogenic cytokine. These data may provide a useful tool to classify a more homogeneous subset of UC patients, allowing for improved diagnostics and targeted therapeutics.
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