Open AccessDistinct IFNG methylation in a subset of ulcerative colitis patients based on reactivity to microbial antigens
Author(s) -
Gonsky Rivkah,
Deem Richard L.,
Landers Carol J.,
Derkowski Carrie A.,
Berel Dror,
McGovern Dermot P.B.,
Targan Stephan R.
Publication year - 2011
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.21352
Subject(s) - immunology , antigen , panca , ulcerative colitis , inflammatory bowel disease , methylation , dna methylation , pathogenesis , serology , antibody , epigenetics , medicine , biology , disease , gene expression , anti neutrophil cytoplasmic antibody , gene , pathology , genetics , vasculitis
Abstract 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‐γ 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‐γ secretion was measured by ELISA. Results: IBD patients requiring surgery exhibited reduced IFNG methylation compared to nonsurgical patients ( P < 0.02). Enhancement of IFN‐γ 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‐γ 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. (Inflamm Bowel Dis 2011;)