Bove K E, Sheridan R, Fei L, Anders R, Chung C T, Cummings O W, Finegold M J, Finn L, Ranganathan S, Kim G, Lovell M, Magid M S, Melin-Aldana H, Russo P, Shehata B, Wang L, White F, Chen Z, Spino C, Magee J C
1 Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
2 Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Pediatr Dev Pathol. 2018 Jan-Feb;21(1):29-40. doi: 10.1177/1093526617707851. Epub 2017 May 5.
We hypothesized that if infection is the proximate cause of congenital biliary atresia, an appropriate response to antigen would occur in lymph nodes contiguous with the biliary remnant. We compared the number of follicular germinal centers (GC) in 79 surgically excised hilar lymph nodes (LN) and 27 incidentally discovered cystic duct LNs in 84 subjects at the time of hepatic portoenterostomy (HPE) for biliary atresia (BA) to autopsy controls from the pancreaticobiliary region of non-septic infants >3 months old at death. All 27 control LN lacked GC, a sign in infants of a primary response to antigenic stimulation. GC were found in 53% of 106 LN in 56 of 84 subjects. Visible surgically excised LN contiguous with the most proximal biliary remnants had 1 or more well-formed reactive GC in only 26/51 subjects. Presence of GC and number of GC/LN was unrelated to age at onset of jaundice or to active fibroplasia in the biliary remnant but was related to older age at HPE. Absent GC in visible and incidentally removed cystic duct LNs predicted survival with the native liver at 2 and 3 years after HPE, P = .03, but significance was lost at longer intervals. The uncommon inflammatory lesions occasionally found in remnants could be secondary either to bile-induced injury or secondary infection established as obstruction evolves. The absence of consistent evidence of antigenic stimulation in LN contiguous with the biliary remnant supports existence of at least 1 major alternative to infection in the etiology of biliary atresia.
我们推测,如果感染是先天性胆道闭锁的直接原因,那么在与胆道残端相邻的淋巴结中会出现对抗原的适当反应。我们比较了84例因胆道闭锁(BA)行肝门空肠吻合术(HPE)时手术切除的79个肝门淋巴结(LN)和27个偶然发现的胆囊管淋巴结中的滤泡生发中心(GC)数量,与3个月以上死亡时无败血症的非婴儿胰胆区域尸检对照。所有27个对照淋巴结均缺乏GC,这是婴儿对抗抗原刺激的初级反应的标志。在84例受试者中的56例的106个淋巴结中,有53%发现了GC。与最近端胆道残端相邻的可见手术切除淋巴结中,只有26/51例受试者有1个或更多形成良好的反应性GC。GC的存在和GC/淋巴结数量与黄疸发作时的年龄或胆道残端的活跃纤维化无关,但与HPE时的年龄较大有关。在可见的和偶然切除的胆囊管淋巴结中缺乏GC预示着HPE后2年和3年肝脏存活,P = 0.03,但在更长时间间隔时显著性消失。在残端偶尔发现的罕见炎性病变可能继发于胆汁诱导的损伤或随着梗阻发展而确立的继发感染。与胆道残端相邻的淋巴结中缺乏一致的抗原刺激证据支持在胆道闭锁病因中至少存在1种感染的主要替代因素。