Department of Gastroenterology, University Hospital of Patras, CP 26504, Patras, Greece.
Department of Pathology, School of Medicine, University of Patras, CP 26504, Patras, Greece.
Dig Dis Sci. 2018 Oct;63(10):2582-2592. doi: 10.1007/s10620-018-5146-9. Epub 2018 Jun 7.
The present study investigates the role of innate and adaptive immune system of intestinal mucosal barrier function in cirrhosis.
Forty patients with decompensated (n = 40, group A), 27 with compensated cirrhosis (n = 27, group B), and 27 controls (n = 27, group C) were subjected to duodenal biopsy. Expression of α-defensins 5 and 6 at the intestinal crypts was evaluated by immunohistochemistry and immunofluorescence. Serum endotoxin, intestinal T-intraepithelial, and lamina propria B-lymphocytes were quantified.
Cirrhotic patients presented higher endotoxin concentrations (p < 0.0001) and diminished HD5 and HD6 expression compared to healthy controls (p = 0.000287, p = 0.000314, respectively). The diminished HD5 and HD6 expressions were also apparent among the decompensated patients compared to compensated group (p = 0.025, p = 0.041, respectively). HD5 and HD6 expressions were correlated with endotoxin levels (r = -0.790, p < 0.0001, r = - 0.777, p < 0.0001, respectively). Although intraepithelial T-lymphocytes were decreased in group A compared to group C (p = 0.002), no notable alterations between groups B and C were observed. The B-lymphocytic infiltrate did not differ among the investigated groups.
These data demonstrate that decreased expression of antimicrobial peptides may be considered as a potential pathophysiological mechanism of intestinal barrier dysfunction in liver cirrhosis, while remodeling of gut-associated lymphoid tissue as an acquired immune response to bio-pathogens remains an open field to illuminate.
本研究旨在探讨肠黏膜屏障功能中固有和适应性免疫系统在肝硬化中的作用。
40 例失代偿性肝硬化患者(n=40,A 组)、27 例代偿性肝硬化患者(n=27,B 组)和 27 例健康对照者(n=27,C 组)接受十二指肠活检。采用免疫组化和免疫荧光法检测肠隐窝α防御素 5 和 6 的表达。定量检测血清内毒素、肠道 T 细胞上皮内和固有层 B 淋巴细胞。
与健康对照组相比,肝硬化患者的内毒素浓度更高(p<0.0001),HD5 和 HD6 的表达降低(p=0.000287,p=0.000314)。与代偿组相比,失代偿组的 HD5 和 HD6 表达也明显降低(p=0.025,p=0.041)。HD5 和 HD6 的表达与内毒素水平呈负相关(r=-0.790,p<0.0001,r=-0.777,p<0.0001)。与 C 组相比,A 组上皮内 T 淋巴细胞减少(p=0.002),但 B 组和 C 组之间无明显差异。各组间 B 淋巴细胞浸润无差异。
这些数据表明,抗菌肽表达降低可能被视为肝硬化肠屏障功能障碍的潜在病理生理机制,而肠道相关淋巴组织的重塑作为对生物病原体的获得性免疫反应仍是一个有待阐明的领域。