Das Prasenjit, Gahlot Gaurav P S, Mehta Ritu, Makharia Archita, Verma Anil K, Sreenivas Vishnubhatla, Panda Subrat K, Ahuja Vineet, Gupta Siddhartha Datta, Makharia Govind K
Department of Pathology and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India; Department of Pathology and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
Dig Liver Dis. 2016 Nov;48(11):1290-1295. doi: 10.1016/j.dld.2016.06.013. Epub 2016 Jun 21.
Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titre and mild enteropathy.
We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies.
Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 and 1) (n=26), advanced enteropathy (Marsh grade ≥2) (n=41) and control biopsies (n=12) were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared.
End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labelling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former.
Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy.
乳糜泻(CeD)中绒毛萎缩的严重程度是肠上皮细胞丢失和细胞再生的累积效应。即使在抗组织转谷氨酰胺酶(tTG)抗体滴度呈阳性且患有轻度肠病的患者中,无麸质饮食也已显示出益处。
我们探讨了轻度和重度肠病中黏膜凋亡性肠上皮细胞丢失与细胞再生之间的平衡。
对轻度肠病(马什分级0和1)患者(n = 26)、重度肠病(马什分级≥2)患者(n = 41)的十二指肠活检标本以及对照活检标本(n = 12)进行免疫组织化学染色,检测凋亡终末标志物(M30、H2AX)、细胞死亡标志物(穿孔素、膜联蛋白V)和细胞增殖标志物(Ki67)。比较基于标志物强度和分布的综合H评分。
与对照组相比,轻度和重度肠病中凋亡终末标志物和细胞死亡标志物(穿孔素)均显著上调;轻度和重度肠病之间无差异。与对照组相比,轻度肠病隐窝中的Ki67标记指数显著更高,表明前者具有持续的再生活性。
即使在轻度肠病患者中,凋亡率也与重度肠病患者相似。这些发现表明有必要重新审视目前不治疗轻度肠病患者的做法。