Al-Masri Abdul Nasser, Flemming Peer, Rodeck Burkhard, Melter Michael, Leonhardt Johannes, Petersen Claus
Department of Pediatric Surgery, Medical School Hannover, 30625 Hannover, Germany.
J Pediatr Surg. 2006 Jun;41(6):1139-43. doi: 10.1016/j.jpedsurg.2006.02.022.
Biliary atresia (BA) is a rare disease of the newborn for which the Kasai procedure is curative only for a few of the patients. The dilemma is that all therapeutic attempts to cure the disease are symptomatic because the etiology is still unclear. One theory suggests a progressive inflammatory process, possibly induced by a viral infection. The aim of the present study was to investigate the activity of type I interferons (IFNs) in the livers of patients with BA. Mx proteins, which mediate an early innate immune response, are a very sensitive marker for type I IFN activity (eg, to viral infection). Liver biopsies were taken during the Kasai procedure from 13 newborns with BA who were serologically negative for hepatotropic viruses. Age-matched controls originated from 7 patients with neonatal cholestasis (eg, inspissated bile syndrome), 3 aborted fetuses, and a 10-year-old child. The immunostaining procedure (alkaline phosphatase anti-alkaline phosphatase) was performed with Mx-specific monoclonal antibody. Immunostaining for Mx proteins was positive in the hepatocytes of all newborns with BA, whereas the intrahepatic bile ducts were positive in all but one. In the control group, 8 of 11 liver samples were Mx-negative. This is the first study dealing with the detection of type I IFN activity in the liver of patients with BA. This observation supports the etiologic consideration of type I IFN-mediated immune response. Although positive findings of viruses in patients with BA are still inconsistent, the present study retraces the progressive inflammatory process in BA one more step toward its beginning.
胆道闭锁（BA）是一种罕见的新生儿疾病，对于该病，葛西手术仅对少数患者具有治愈作用。困境在于，由于病因仍不明确，所有治疗该疾病的尝试都只是对症治疗。一种理论认为这是一个渐进性的炎症过程，可能由病毒感染引发。本研究的目的是调查BA患者肝脏中I型干扰素（IFN）的活性。Mx蛋白介导早期固有免疫反应，是I型IFN活性（如对病毒感染）的非常敏感的标志物。在葛西手术期间，从13例血清学检查嗜肝病毒呈阴性的BA新生儿中获取肝脏活检样本。年龄匹配的对照组来自7例新生儿胆汁淤积（如浓缩胆汁综合征）患者、3例流产胎儿和一名10岁儿童。使用Mx特异性单克隆抗体进行免疫染色程序（碱性磷酸酶抗碱性磷酸酶）。所有BA新生儿的肝细胞中Mx蛋白免疫染色均为阳性，而除1例之外的所有肝内胆管均为阳性。在对照组中，11个肝脏样本中有8个Mx呈阴性。这是第一项关于检测BA患者肝脏中I型IFN活性的研究。这一观察结果支持了I型IFN介导的免疫反应的病因学考量。尽管在BA患者中病毒阳性结果仍不一致，但本研究在BA渐进性炎症过程的起始方向上又向前追溯了一步。
