Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients
Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients
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DOI：
10.1136/gut.2005.086413
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发表时间：
2006-07-01
期刊：
影响因子：
24.5
通讯作者：
Rhodes, J. M.
中科院分区：
文献类型：
--
作者：
Bodger, K.;Halfvarson, J.;Rhodes, J. M.
背景和目标：先前对患有炎症性肠病（IBD）的单卵双胞胎结肠粘蛋白的色谱分析表明溃疡性结肠炎（UC）中存在遗传粘蛋白改变。本研究探讨了这一点，进一步通过评估粘膜表达的癌胚糖抗原TF（半乳糖β 1，3 N-乙酰半乳糖胺α-），在相同的IBD twin.Materials和方法：福尔马林固定石蜡包埋直肠活检研究了22个单卵双胞胎对IBD。其中包括8对UC双胞胎和14对克罗恩病（CD）双胞胎，其中6对疾病一致，16对未受影响的双胞胎兄弟姐妹。密切相邻的部分进行了评估，花生凝集素组织化学TF表达和核因子κ B（NF κ B B）激活与调查人员盲目的diagnosis.Results：未受影响的双胞胎几乎所有TF阳性（15/16）相比，5/29组织学正常对照组（p < 0.0001）。未发病的UC（7/8）和CD双胞胎（8/8）的TF阳性相似。TF阳性主要局限于浅表上皮，而不存在于下隐窝的干细胞室，这表明糖基化变化是后天的，而不是遗传决定的。活化的NF κ B存在于13/14例未受影响的IBD双胞胎的粘膜活检组织的表面上皮中，但仅存在于6/22例组织学正常的对照中（p=0.0004）。所有22例IBD双胞胎TF阳性，18例活化NF κ B B阳性。结论：IBD患者的正常同卵双胞胎的粘膜糖基化改变在这项研究中得到证实。这发生在UC和CD双胞胎中。这些变化可能是获得性的而不是先天性的，可能反映了“炎症前”NF κ B的激活。
Background and aims: Previous chromatographic analysis of colonic mucins from monozygotic twins with inflammatory bowel disease (IBD) suggested a genetic mucin alteration in ulcerative colitis (UC). This study explores this further by assessing mucosal expression of the oncofetal carbohydrate antigen TF (galactose beta 1, 3 N-acetylgalactosamine alpha-), among the same IBD twins.Materials and methods: Formalin fixed paraffin embedded rectal biopsies were studied from 22 monozygotic twin pairs with IBD. These included eight UC twin pairs and 14 Crohn's disease (CD) twin pairs, with six pairs concordant for disease and 16 unaffected twin siblings. Closely adjacent sections were assessed by peanut lectin histochemistry for TF expression and immunohistochemically for nuclear factor kappa B (NF kappa B) activation with investigators blinded to the diagnosis.Results: Unaffected twins were almost all TF positive (15/16) compared with 5/29 histologically normal controls (p < 0.0001). Unaffected UC (7/8) and CD twins (8/8) were similarly TF positive. TF positivity was confined mainly to the superficial epithelium and absent from the stem cell compartment of the lower crypts, suggesting that glycosylation changes are acquired rather than genetically determined. Activated NF kappa B was present in the surface epithelium of mucosal biopsies from 13/14 unaffected IBD twins but in only 6/22 histologically normal controls (p=0.0004). All 22 affected IBD twins were TF positive and 18 were positive for activated NF kappa B.Conclusions: Altered mucosal glycosylation in unaffected identical twins of IBD patients was confirmed in this study. This occurred in both UC and CD twins. The changes are probably acquired rather than congenital and may reflect "preinflammatory" NF kappa B activation.