Objectives Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive ‘normal’ IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. Design The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. Results The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2–88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. Conclusion Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose–response by IEL to environmental (gluten) antigenic influence.

中文翻译：

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ROC-king 起：上皮内淋巴细胞计数、分布和在乳糜泻黏膜解释中的作用

目的 上皮内淋巴细胞 (IEL) 计数是乳糜泻 (CD) 组织学诊断的核心，但尚未公布明确的“正常”IEL 范围。在这项多中心研究中，受试者工作特征 (ROC) 曲线分析用于确定正常和 CD（Marsh III 病变）十二指肠粘膜之间的最佳截断值，基于对 >400 个粘膜活检标本的 IEL 计数。设计 该研究是在 2015 年布加勒斯特国际消化病理学会议上设计的。来自三大洲八个国家的 19 个中心的研究人员招募了 198 名 Marsh III 组织学患者和 203 名对照患者，并使用一个商定的方案对孔中的 IEL/100 肠细胞进行计数定向十二指肠活检。还收集了人口统计学和血清学数据。结果 CD组和对照组平均年龄为45岁。5 岁（新生儿至 82 岁）和 38.3 岁（2-88 岁）。CD 中平均 IEL 计数为 54±18/100 肠上皮细胞，正常对照中为 13±8 (p=0.0001)。ROC 分析表明最佳截止点为 25 IEL/100 肠细胞，具有 99% 的敏感性、92% 的特异性和 99.5% 的曲线下面积。其他介于 20 到 40 IEL 之间的分界线的歧视性较小。此外，有足够多的活组织检查来探索 Marsh III 病变子分类中的 IEL 计数。结论 我们的 ROC 曲线分析表明，对于 Marsh III 病变，25 IEL/100 肠细胞的临界值可优化正常对照和 CD 活检之间的区分。在 Marsh III a、b 和 c 病变之间未发现 IEL 计数差异。有迹象表明 IEL 对环境（麸质）抗原影响的剂量反应连续分级。