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粪便M2型丙酮酸激酶(M2-PK):一种新型肠道炎症标志物。

Fecal M2-pyruvate kinase (M2-PK): a novel marker of intestinal inflammation.

作者信息

Chung-Faye Guy, Hayee Bu'hussain, Maestranzi Susan, Donaldson Nora, Forgacs Ian, Sherwood Roy

机构信息

Department of Gastroenterology, King's College Hospital, London, UK.

出版信息

Inflamm Bowel Dis. 2007 Nov;13(11):1374-8. doi: 10.1002/ibd.20214.

DOI:10.1002/ibd.20214
PMID:17577247
Abstract

BACKGROUND

Surrogate markers of bowel inflammation are increasingly being recognized as important, not only as markers of disease activity in inflammatory bowel disease (IBD) but also to differentiate irritable bowel syndrome (IBS) from IBD. The dimeric M2-isoform of pyruvate kinase (M2-PK) has been reported to be elevated in fecal specimens from colorectal cancer (CA) patients, but its role in IBD is unknown. This study investigated the usefulness of fecal M2-PK in cohorts of patients with IBD, IBS, and CA.

METHODS

Stool samples were obtained for calprotectin and M2-PK measurements in patients with previously diagnosed IBD or new patients being investigated for lower gastrointestinal (GI) symptoms in a UK university hospital. Other investigations were performed as directed by the investigating physician and patients with known IBD were assessed for disease activity by a physician global assessment, Harvey-Bradshaw index (HBI), or endoscopic grading.

RESULTS

Fecal M2-PK and calprotectin measurements were obtained for 148 patients: 50 with ulcerative colitis (UC); 31 with Crohn's disease (CD), 43 with irritable bowel syndrome/functional bowel disorders (IBS); 7 with colorectal CA, and 17 with miscellaneous conditions (excluded from the analysis). Median M2-PK values (U/mL) were significantly elevated in UC: 20.0 (95% confidence interval [CI] 5.4-69.0, P < 0.0001), CD: 24.3 (95% CI 6.4-44.0, P < 0.0001), and CA: 7.0 (95% CI 4.3-88.0, P < 0.0006) compared to IBS: 0.1 (95% CI 0.0-3.2). There was a strong linear correlation of M2-PK with calprotectin levels. A predetermined cutoff level of 3.7 U/mL for a normal M2-PK test produced a sensitivity, specificity, and positive predictive value (PPV) of 73%, 74%, and 89%, respectively, for organic disease. Furthermore, M2-PK levels were significantly elevated in active, compared to inactive, disease for CD (30 versus 0.55 U/mL, P < 0.005) and UC (40 versus 1.2 U/mL, P = 0.006), respectively.

CONCLUSIONS

Fecal M2-PK is elevated in IBD as well as in CA patients and is a sensitive and relatively specific marker for organic GI pathology, with a PPV of 89%. Furthermore, it appears to be a potentially valuable, noninvasive marker of disease activity in IBD.

摘要

背景

肠道炎症的替代标志物越来越被认为很重要,不仅作为炎症性肠病(IBD)疾病活动的标志物,还用于区分肠易激综合征(IBS)和IBD。据报道,丙酮酸激酶的二聚体M2同工型(M2-PK)在结直肠癌(CA)患者的粪便样本中升高,但其在IBD中的作用尚不清楚。本研究调查了粪便M2-PK在IBD、IBS和CA患者队列中的实用性。

方法

在英国一家大学医院,对先前诊断为IBD的患者或因下消化道(GI)症状接受调查的新患者采集粪便样本,用于测量钙卫蛋白和M2-PK。其他检查由调查医生指导进行,已知患有IBD的患者由医生进行整体评估、哈维-布拉德肖指数(HBI)或内镜分级来评估疾病活动度。

结果

对148例患者进行了粪便M2-PK和钙卫蛋白测量:50例溃疡性结肠炎(UC)患者;31例克罗恩病(CD)患者,43例肠易激综合征/功能性肠病(IBS)患者;7例结直肠癌患者,17例患有其他病症(排除在分析之外)。与IBS患者的0.1(95%置信区间[CI]0.0 - 3.2)相比,UC患者的M2-PK中位数(U/mL)显著升高:20.0(95%CI 5.4 - 69.0,P < 0.0001),CD患者为24.3(95%CI 6.4 - 44.0,P < 0.0001),CA患者为7.0(95%CI 4.3 - 88.

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