Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan.
J Pediatr Gastroenterol Nutr. 2011 Dec;53(6):620-6. doi: 10.1097/MPG.0b013e3182307c9c.
Inappropriate host immunological reactions against unknown ligands via the Toll-like receptor (TLR) cascades may trigger progressive inflammatory biliary destruction that manifests as biliary atresia (BA) in newborns or infants. The aim of the study was to clarify the role of the innate immune system in the development of BA.
Liver tissue was obtained from 49 patients with pediatric hepatobiliary diseases: 19 with BA, 21 with choledochal cysts, and 9 with other hepatobiliary diseases. BA samples obtained during the initial portoenterostomy and reoperation or liver transplantation (LT) were classified as early and late BA groups, respectively. Of the early BA group, those requiring LT were designated as the LT group, and the others were designated as the non-LT group. The mRNA expression levels of TLRs 2, 3, 4, 7, and 8 were determined by real-time quantitative reverse transcription-polymerase chain reaction and were compared between groups. The correlation between TLR mRNA expression level and age at sampling was examined for each TLR in the patients with BA.
TLR8 mRNA, encoding the receptor for single-stranded RNA, was significantly higher in the early BA group, compared with non-BA groups (P = 0.008). Within the BA group, mRNA levels of TLRs 2 and 8 were significantly higher in the early group than in the late group (P = 0.02 and 0.006, respectively), despite there being no significant correlation between TLR mRNA expression and age at sampling, except for TLR7 (r = 0.77, P = 0.001). Compared with the non-LT group, the LT group demonstrated significantly higher mRNA expression of TLRs 3 and 7 (P = 0.02 and 0.01, respectively).
Innate immune responses may contribute to the initiation and progression of BA. Severe inflammation characteristic of BA around the time of the first operation may abate postoperatively, but determination of selected TLR mRNA expression levels in the liver at the time of Kasai portoenterostomy may assist in predicting the prognosis of patients with BA.
通过 Toll 样受体（TLR）级联反应，宿主对未知配体的不适当免疫反应可能引发进行性炎症性胆道破坏，表现为新生儿或婴儿的胆道闭锁（BA）。本研究旨在阐明固有免疫系统在 BA 发展中的作用。
从 49 例儿科肝胆疾病患者的肝组织中获得标本：19 例 BA，21 例胆总管囊肿，9 例其他肝胆疾病。在初次门腔分流术和再次手术或肝移植（LT）时获得的 BA 样本分别归类为早期和晚期 BA 组。在早期 BA 组中，需要 LT 的患者被指定为 LT 组，其余患者被指定为非 LT 组。通过实时定量逆转录-聚合酶链反应（qRT-PCR）测定 TLRs 2、3、4、7 和 8 的 mRNA 表达水平，并对各组之间进行比较。对 BA 患者的每个 TLR 进行 TLR mRNA 表达水平与采样年龄之间的相关性分析。
TLR8mRNA 编码单链 RNA 的受体，在早期 BA 组中明显高于非 BA 组（P=0.008）。在 BA 组中，早期组 TLRs 2 和 8 的 mRNA 水平明显高于晚期组（P=0.02 和 0.006），尽管 TLR mRNA 表达与采样年龄之间没有显著相关性，除 TLR7 外（r=0.77，P=0.001）。与非 LT 组相比，LT 组 TLRs 3 和 7 的 mRNA 表达明显升高（P=0.02 和 0.01）。
固有免疫反应可能有助于 BA 的启动和进展。第一次手术时 BA 特征性的严重炎症可能在术后减轻，但在进行 Kasai 门腔分流术时测定肝内选定 TLR mRNA 表达水平可能有助于预测 BA 患者的预后。
