Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.
National Institute for Mother and Child Health, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.
Dig Dis Sci. 2021 Oct;66(10):3352-3358. doi: 10.1007/s10620-020-06680-x. Epub 2020 Nov 3.
The histopathologic diagnosis of celiac disease (CD) may be challenging when the duodenal biopsies mucosal injury is limited. Intraepithelial T-lymphocytes (IELs) can be useful to characterize the degree of mucosal inflammation. A small fraction of IELs expresses the γδ T-cell receptor (named γδ-IELs), whose density, determined by flow cytometry or frozen section immunohistochemistry (IHC), is a specific marker for CD.
To establish a new IHC assay for γδ-IELs applicable to formalin-fixed paraffin-embedded (FFPE) duodenal biopsies.
We analyzed γδ-IELs using IHC in 138 duodenal biopsies using a standard IHC staining protocol with a new monoclonal antibody H-41. IELs were quantitated with digital image analysis.
Compared to those in non-celiac controls (n = 51), γδ-IEL density was significantly increased in newly diagnosed celiac disease patients (n = 22, p < 0.0001). In ROC-curve analysis, the cutoff of 6.5 γδ-IELs/100 enterocytes distinguished optimally active CD patients from non-celiac controls (sensitivity 96%, specificity 95%). γδ-IEL density in CD patients on a gluten-free diet (n = 53) were also higher than in controls (p < 0.0001), but lower than those in newly diagnosed CD (p < 0.0001). The diagnostic value of γδ-IELs outperformed that of CD3 + IELs in both patient groups. γδ-IELs were better than CD3 + IELs distinguishing between celiac disease and conditions histologically mimicking celiac disease (n = 12).
Intraepithelial γδ T-lymphocytes can be stained and quantitated reliably in FFPE duodenal biopsies. The results showed excellent specificity and sensitivity for celiac disease. The new IHC method of detection of γδ-IELs is a promising addition to the routine histopathologic assessment methodology of celiac disease.
当十二指肠活检的黏膜损伤有限时，对乳糜泻（CD）的组织病理学诊断可能具有挑战性。上皮内 T 淋巴细胞（IEL）可用于表征黏膜炎症程度。一小部分 IEL 表达γδ T 细胞受体（称为γδ-IEL），其密度可通过流式细胞术或冷冻切片免疫组织化学（IHC）确定，是 CD 的特异性标志物。
建立一种适用于福尔马林固定石蜡包埋（FFPE）十二指肠活检的新的γδ-IELs IHC 检测方法。
我们使用新的单克隆抗体 H-41 通过标准 IHC 染色方案在 138 例十二指肠活检中分析γδ-IELs。使用数字图像分析定量 IEL。
与非乳糜泻对照组（n=51）相比，新诊断的乳糜泻患者（n=22，p<0.0001）的γδ-IEL 密度显著增加。在 ROC 曲线分析中，6.5 个γδ-IEL/100 肠上皮细胞的截定点最佳地区分活动性 CD 患者和非乳糜泻对照组（敏感性 96%，特异性 95%）。无麸质饮食的 CD 患者（n=53）的γδ-IEL 密度也高于对照组（p<0.0001），但低于新诊断的 CD 患者（p<0.0001）。在两组患者中，γδ-IEL 的诊断价值均优于 CD3+IEL。γδ-IEL 比 CD3+IEL 更能区分乳糜泻和组织学上类似乳糜泻的疾病（n=12）。
在 FFPE 十二指肠活检中，上皮内 γδ T 淋巴细胞可可靠染色和定量。结果显示对乳糜泻具有极好的特异性和敏感性。检测γδ-IEL 的新 IHC 方法是对乳糜泻常规组织病理学评估方法的有前途的补充。
