S Gahlot Gaurav P, Das Prasenjit, Baloda Vandana, Singh Alka, Vishnubhatla Sreenivas, Gupta Siddhartha Datta, Makharia Govind K
Department of Pathology, AIIMS, New Delhi, India.
Department of Gastroenterology and Human Nutritions, AIIMS, New Delhi, India.
Indian J Pathol Microbiol. 2019 Jul-Sep;62(3):399-404. doi: 10.4103/IJPM.IJPM_703_18.
It is hypothesized that the duodenal mucosal damage in patients with celiac disease (CeD) is caused by the mucosa-infiltrating lymphoid cells. This study aimed to analyze the immune effective and regulatory T (Treg) cells in duodenal biopsies from treatment-naive adult patients with CeD having different histological grades and controls.
Dual-color immunohistochemical staining was done in a total of 234 duodenal biopsies, including 132 controls and 102 adult patients with CeD using CD20, CD3:CD4, CD3:CD8, CD4:FoxP3, CD8:FoxP3, and TCRαβ:TCRγδ antibodies. The density of these lymphoid cells in lamina propria and mucosal epithelium was compared between controls and CeD, with different modified Marsh grades.
Densities of CD4+ T cells in lamina propria and CD8+γδ intraepithelial lymphocytes (IELs) were significantly more in biopsies from patients with CeD, than in controls. An increasing linear pattern of IELs, CD3+ T cells, and CD20+ B cells was observed with increasing grades of villous abnormalities. Although CD8+ FoxP3+ Treg cells were significantly more in biopsies from patients with CeD, there was no significant difference in CD4+ FoxP3+ Treg cell infiltrate between both the groups.
Our finding in this observational study generates interest to study the local intestinal mucosal immunity in CeD in detail. A study to prove the failure of CD4+ FoxP3+ Treg cell recruitment in CeD and its direct functional impact may yield valuable information regarding loss of mucosal tolerance.
据推测，乳糜泻（CeD）患者的十二指肠黏膜损伤是由浸润黏膜的淋巴细胞引起的。本研究旨在分析未经治疗的成年CeD患者十二指肠活检组织中具有不同组织学分级的免疫效应细胞和调节性T（Treg）细胞，并与对照组进行比较。
使用CD20、CD3:CD4、CD3:CD8、CD4:FoxP3、CD8:FoxP3和TCRαβ:TCRγδ抗体，对总共234份十二指肠活检组织进行双色免疫组化染色，其中包括132例对照和102例成年CeD患者。比较对照组和不同改良马什分级的CeD患者固有层和黏膜上皮中这些淋巴细胞的密度。
CeD患者活检组织中固有层CD4 + T细胞和CD8 + γδ上皮内淋巴细胞（IELs）的密度显著高于对照组。随着绒毛异常程度的增加，观察到IELs、CD3 + T细胞和CD20 + B细胞呈线性增加。虽然CeD患者活检组织中CD8 + FoxP3 + Treg细胞明显更多，但两组之间CD4 + FoxP3 + Treg细胞浸润无显著差异。
我们在这项观察性研究中的发现引发了对详细研究CeD患者局部肠道黏膜免疫的兴趣。一项关于证明CeD中CD4 + FoxP3 + Treg细胞募集失败及其直接功能影响的研究，可能会产生有关黏膜耐受性丧失的有价值信息。
