What Causes Biliary Atresia? Unique Aspects of the Neonatal Immune System Provide Clues to Disease Pathogenesis.
What Causes Biliary Atresia? Unique Aspects of the Neonatal Immune System Provide Clues to Disease Pathogenesis.
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DOI：
10.1016/j.jcmgh.2015.04.001
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发表时间：
2015-05-01
影响因子：
7.2
通讯作者：
Mack, Cara L
中科院分区：
文献类型：
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作者：
Mack, Cara L
胆道闭锁（BA）是新生儿胆汁淤积症最常见的可识别原因，大多数患者需要肝移植才能生存。尽管Kasai门肠造口术进行了手术干预，但在生命早期仍会出现明显的纤维化和肝硬化。对炎症性纤维化胆管病病因的进一步了解将导致旨在保护肝内胆道系统免受免疫介导损伤的治疗。本文综述了适应性免疫反应在胆管损伤中的作用，包括细胞免疫和体液免疫。新生儿BA的表现提示了一个问题，即新生儿免疫系统独特方面的哪些潜在改变为进行性胆道疾病奠定了基础。本文还讨论了新生儿免疫反应的特点，以及这种反应的改变如何导致BA发病的理论。这些包括异常的1型辅助性T细胞（TH1）和TH17反应，调节性T细胞的缺陷，体液免疫的激活和自身免疫。为了提高我们对BA病因的理解，未来的研究应该集中在新生儿免疫系统出现问题的独特方面。
Biliary atresia (BA) is the most frequent identifiable cause of neonatal cholestasis, and the majority of patients will need liver transplantation for survival. Despite surgical intervention with the Kasai portoenterostomy, significant fibrosis and cirrhosis develop early in life. An increased understanding of what causes this inflammatory fibrosing cholangiopathy will lead to therapies aimed at protecting the intrahepatic biliary system from immune-mediated damage. This review focuses on studies pertaining to the role of the adaptive immune response in bile duct injury in BA, including cellular and humoral immunity. The neonatal presentation of BA prompts the question of what potential modifications of unique aspects of the neonatal immune system set the stage for the progressive biliary disease. This review also discusses the characteristics of neonatal immune response and the theories on how alterations of this response could contribute to the pathogenesis of BA. These include aberrant type 1 helper T-cell (TH1) and TH17 responses, deficiencies in regulatory T cells, activation of humoral immunity, and autoimmunity. To advance our understanding of the etiology of BA, future studies should focus on the unique aspects of the neonatal immune system that have gone awry.