Altered Expression of the Epithelial Mucin MUC1 Accompanies Endoscopic Recurrence of Postoperative Crohn's Disease.
Altered Expression of the Epithelial Mucin MUC1 Accompanies Endoscopic Recurrence of Postoperative Crohn's Disease.
复制标题
上皮粘蛋白 MUC1 表达的改变伴随着术后克罗恩病的内镜复发。
DOI：
10.1097/mcg.0000000000001340
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发表时间：
2021
影响因子：
2.9
通讯作者：
Finn,OliveraJ
中科院分区：
文献类型：
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作者：
Hashash,JanaG;Beatty,PamelaL;Critelli,Kristen;Hartman,DouglasJ;Regueiro,Matthew;Tamim,Hani;Regueiro,MiguelD;Binion,DavidG;Finn,OliveraJ
背景：muc1糖蛋白在上皮细胞上以低水平和完全糖基化的形式表达。炎症导致MUC1过表达和低糖基化。我们假设在克罗恩病（CD）术后复发中会发现低糖基化MUC1的过表达，并且可以被认为是复发严重程度的另一个生物标志物。方法：我们检查了先前进行回盲切除术的患者的新末端回肠活检，这些患者术后进行了CD复发的内镜评估，并给出了Rutgeerts回肠复发评分。使用2种不同的抗MUC1抗体对连续的组织切片进行染色，HMPV识别所有形式的MUC1, 4H5仅识别炎症相关的低糖基化MUC1。结果：共对71例术后CD患者进行了评估。内镜下CD严重复发患者（i3+ i4）、回肠评分i2中MUC1糖基化/正常（P< 0.0001）和低糖基化/异常（P< 0.0001）表达均明显高于内镜下缓解患者（i0+ i1）。无论是否使用抗tnf -α，结果相似。尽管MUC1表达和Rutgeerts评分在大多数病例中是一致的，但也有少数例外，MUC1表达的特征比Rutgeerts评分所暗示的复发更严重。结论：在CD术后复发患者的新末端回肠组织中MUC1过表达和低糖基化。升高的水平与更严重的内镜下复发评分相关，这与使用抗tnf -α无关。Rutgeerts评分和MUC1表达之间的差异表明，添加MUC1作为术后CD复发严重程度的生物标志物可能改善复发状态的分类，从而改善治疗决策。
Background:MUC1-glycoprotein is expressed at low levels and in fully glycosylated form on epithelial cells. Inflammation causes MUC1 overexpression and hypoglycosylation. We hypothesized that overexpression of hypoglycosylated MUC1 would be found in postoperative Crohn’s disease (CD) recurrence and could be considered an additional biomarker of recurrence severity.Methods:We examined archived neo-terminal ileum biopsies from patients with prior ileocecal resection who had postoperative endoscopic assessment of CD recurrence and given a Rutgeerts ileal recurrence score. Consecutive tissue sections were stained using 2 different anti-MUC1 antibodies, HMPV that recognizes all forms of MUC1 and 4H5 that recognizes only inflammation-associated hypoglycosylated MUC1.Results:A total of 71 postoperative CD patients were evaluated. There was significant increase in MUC1 expression of both glycosylated/normal (P< 0.0001) and hypoglycosylated/abnormal (P< 0.0001) forms in patients with severe endoscopic CD recurrence (i3+ i4), ileal score i2, compared with patients in endoscopic remission (i0+ i1). Results were similar regardless of anti-TNF-α use. Although MUC1 expression and Rutgeerts scores were in agreement when characterizing the majority of cases, there were a few exceptions where MUC1 expression was characteristic of more severe recurrence than implied by Rutgeerts score.Conclusions:MUC1 is overexpressed and hypoglycosylated in neo-terminal ileum tissue of patients with postoperative CD recurrence. Increased levels are associated with more severe endoscopic recurrence scores, and this is not influenced by anti-TNF-α use. Discrepancies found between Rutgeerts scores and MUC1 expression suggest that addition of MUC1 as a biomarker of severity of postoperative CD recurrence may improve categorization of recurrence status and consequently treatment decisions.