Distinct IFNG methylation in a subset of ulcerative colitis patients based on reactivity to microbial antigens.
Distinct IFNG methylation in a subset of ulcerative colitis patients based on reactivity to microbial antigens.
复制标题
DOI：
10.1002/ibd.21352
复制
发表时间：
2011-01
影响因子：
4.9
通讯作者：
Targan, Stephan R.
中科院分区：
文献类型：
--
作者：
Gonsky, Rivkah;Deem, Richard L.;Landers, Carol J.;Derkowski, Carrie A.;Berel, Dror;McGovern, Dermot P. B.;Targan, Stephan R.
克罗恩病患者对微生物抗原的高抗体反应性预示着疾病的病程更具侵袭性。然而，很少溃疡性结肠炎患者对微生物抗原表现出血清学反应性。IFN-γ的粘膜表达在IBD的发病机制中起关键作用。最近的GWAS令人惊讶地将UC，而非CD，风险位点与IFNG联系起来。我们最近证明，与对照组相比，IBD患者的粘膜T细胞表现出不同的IFNG甲基化模式。本研究评估了IBD患者外周血T细胞中IFNG甲基化与血清学和临床特征之间的关系。对163名IBD患者（94名CD和64名UC）和43名对照者的外周T细胞DNA进行了8个IFNG位点的甲基化分析。ELISA法检测血清标志物ASCA、OmpC、I2、cir、pANCA。ELISA法检测IFN-γ分泌。与非手术患者相比，需要手术的IBD患者IFNG甲基化水平降低（p<0.02）。UC患者IFN-γ分泌增强（p<0.003），以及针对多种微生物抗原的高抗体反应（p<0.017），与IFNG甲基化降低相关，而CD患者则没有。pANCA水平与IFNG甲基化无关。IFNG甲基化水平与UC患者对微生物成分的免疫反应和IFN-γ的表达相关。血清学和表观遗传标记确定UC患者的一个亚群与关键的TH1致病细胞因子的表达谱。这些数据可能提供一个有用的工具，以分类更均匀的UC患者亚群，从而改进诊断和靶向治疗。
High antibody reactivity toward microbial antigens in Crohn’s disease patients is predictive of a more aggressive disease course. However, few ulcerative colitis patients exhibit serologic reactivity towards microbial antigens. Mucosal expression of IFN-γ plays a pivotal role in IBD pathogenesis. Recent 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. DNA from peripheral T cells of 163 IBD patients (94 CD and 64 UC) and 43 controls was analyzed for methylation of eight IFNG sites. Serum markers ASCA, OmpC, I2, CBir and pANCA were measured by ELISA. IFN-γ secretion was measured by ELISA. IBD patients requiring surgery exhibited reduced IFNG methylation compared to non-surgical 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. 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.
登录
查看更多内容
DOI：
10.1016/j.cgh.2008.04.032
发表时间：
2008-10
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
Dubinsky MC;Kugathasan S;Mei L;Picornell Y;Nebel J;Wrobel I;Quiros A;Silber G;Wahbeh G;Katzir L;Vasiliauskas E;Bahar R;Otley A;Mack D;Evans J;Rosh J;Hemker MO;Leleiko N;Crandall W;Langton C;Landers C;Taylor KD;Targan SR;Rotter JI;Markowitz J;Hyams J;Western Regional Pediatric IBD Research Alliance;Pediatric IBD Collaborative Research Group;Wisconsin Pediatric IBD Alliance
通讯作者：
Wisconsin Pediatric IBD Alliance
影响因子：
30.8
作者：
Fisher, Sheila A.;Tremelling, Mark;Anderson, Carl A.;Gwilliam, Rhian;Bumpstead, Suzannah;Prescott, Natalie J.;Nimmo, Elaine R.;Massey, Dunecan;Berzuini, Carlo;Johnson, Christopher;Barrett, Jeffrey C.;Cummings, Fraser R.;Drummond, Hazel;Lees, Charlie W.;Onnie, Clive M.;Hanson, Catherine E.;Blaszczyk, Katarzyna;Inouye, Mike;Ewels, Philip;Ravindrarajah, Radhi;Keniry, Andrew;Hunt, Sarah;Carter, Martyn;Watkins, Nick;Ouwehand, Willem;Lewis, Cathryn M.;Cardon, Lon;Lobo, Alan;Forbes, Alastair;Sanderson, Jeremy;Jewell, Derek P.;Mansfield, John C.;Deloukas, Panos;Mathew, Christopher G.;Parkes, Miles;Satsangi, Jack
通讯作者：
Satsangi, Jack
影响因子：
30.8
作者：
Imielinski, Marcin;Baldassano, Robert N.;Griffiths, Anne;Russell, Richard K.;Annese, Vito;Dubinsky, Marla;Kugathasan, Subra;Bradfield, Jonathan P.;Walters, Thomas D.;Sleiman, Patrick;Kim, Cecilia E.;Muise, Aleixo;Wang, Kai;Glessner, Joseph T.;Saeed, Shehzad;Zhang, Haitao;Frackelton, Edward C.;Hou, Cuiping;Flory, James H.;Otieno, George;Chiavacci, Rosetta M.;Grundmeier, Robert;Castro, Massimo;Latiano, Anna;Dallapiccola, Bruno;Stempak, Joanne;Abrams, Debra J.;Taylor, Kent;McGovern, Dermot;Heyman, Melvin B.;Ferry, George D.;Kirschner, Barbara;Lee, Jessica;Essers, Jonah;Grand, Richard;Stephens, Michael;Levine, Arie;Piccoli, David;Van Limbergen, Johan;Cucchiara, Salvatore;Monos, Dimitri S.;Guthery, Stephen L.;Denson, Lee;Wilson, David C.;Grant, Struan F. A.;Daly, Mark;Silverberg, Mark S.;Satsangi, Jack;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
影响因子：
30.8
作者：
Hampe, Jochen;Franke, Andre;Schreiber, Stefan
通讯作者：
Schreiber, Stefan
影响因子：
29.4
作者：
Landers, CJ;Cohavy, O;Targan, SR
通讯作者：
Targan, SR