Department of Pathology, University of Oulu, Oulu, Finland.
J Pediatr Gastroenterol Nutr. 2012 Apr;54(4):525-31. doi: 10.1097/MPG.0b013e318237c145.
The aim of the study was to explore pathogenesis and find new serum markers for cow's-milk-sensitive enteropathy (CMSE) and coeliac disease (CD). We assessed the intestinal expression and serum concentration of CD23, IL-15, and FasL. We hypothesised that the serum levels of CD23, a protein expressed in the lymphoid follicles, would be associated with lymphonodular hyperplasia (LNH), a feature characteristic of CMSE. We also presumed that interleukin (IL)-15 and FasL, functionally connected with proliferation and apoptosis of the intraepithelial lymphocytes (IELs), would relate with the increased numbers of IELs present in both CMSE and CD.
Twenty-three children with CMSE, 20 with untreated CD, and 14 controls were studied for CD3, α/β- and γ/δ-expressing IELs, and for duodenal and ileal expression of CD23, FasL, and IL-15 by immunohistochemistry, and for serum concentration of sCD23, sFasL, and sIL-15 by enzyme-linked immunosorbent assay.
There was a trend for increase in sCD23 serum levels in untreated CMSE and in CD (P = 0.074; P = 0.077). CD23 was expressed in the mucosal germinal centres, but sCD23 was not related to presence of LNH. In CMSE, there was a trend for increase in serum sFasL (P = 0.07) and high levels associated with LNH (P = 0.025) and correlated with the IEL numbers (P < 0.05). Mucosal high endothelial venules adjacent to lymphoid follicles showed an intensive FasL expression.
Serum sCD23 shows a trend of increment in CMSE and CD, and in the latter, sCD23 level may provide information about the severity of villous atrophy. In CMSE, high serum sFasL indicates both LNH and an increase of IELs, suggesting importance of FasL-mediated mechanisms in the pathogenesis of these features characteristic of CMSE. Further studies are necessary to evaluate whether intensive FasL expression in mucosal high endothelial venules presents a regulatory element in mucosal immunity.
本研究旨在探讨发病机制,并寻找新的牛乳敏感肠病(CMSE)和乳糜泻(CD)的血清标志物。我们评估了 CD23、IL-15 和 FasL 的肠道表达和血清浓度。我们假设,在淋巴滤泡中表达的蛋白质 CD23 的血清水平与 LNH 有关,LNH 是 CMSE 的特征性特征。我们还推测,与上皮内淋巴细胞(IEL)增殖和凋亡功能相关的白细胞介素(IL)-15 和 FasL 与 CMSE 和 CD 中存在的 IEL 数量增加有关。
研究了 23 例 CMSE 患儿、20 例未经治疗的 CD 患儿和 14 例对照者的 CD3、α/β-和 γ/δ-表达的 IEL,以及免疫组化检测十二指肠和回肠 CD23、FasL 和 IL-15 的表达,以及酶联免疫吸附试验检测血清可溶性 CD23(sCD23)、sFasL 和 sIL-15 的浓度。
未经治疗的 CMSE 和 CD 患儿的 sCD23 血清水平呈上升趋势(P=0.074;P=0.077)。CD23 在黏膜生发中心表达,但 sCD23 与 LNH 无关。在 CMSE 中,血清 sFasL 呈上升趋势(P=0.07),高水平与 LNH 相关(P=0.025),并与 IEL 数量相关(P<0.05)。邻近淋巴滤泡的黏膜高内皮静脉显示 FasL 表达强烈。
血清 sCD23 在 CMSE 和 CD 中呈上升趋势,在后者中,sCD23 水平可能提供关于绒毛萎缩严重程度的信息。在 CMSE 中,高血清 sFasL 表明 LNH 和 IEL 增加,表明 FasL 介导的机制在这些 CMSE 特征性特征的发病机制中很重要。需要进一步研究以评估黏膜高内皮静脉中 FasL 的强烈表达是否代表黏膜免疫的调节因素。