Dubruc Estelle, Nadaud Béatrice, Ruchelli Eduardo, Heissat Sophie, Baruteau Julien, Broué Pierre, Debray Dominique, Cordier Marie-Pierre, Miossec Pierre, Russo Pierre, Collardeau-Frachon Sophie
Department of pathology, Hôpital Femme-Mère-Enfant, CHU de Lyon, France.
Department of pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Pediatr Res. 2017 May;81(5):712-721. doi: 10.1038/pr.2017.8. Epub 2017 Jan 13.
Neonatal hemochromatosis caused by a gestational alloimmune mechanism or gestational alloimmune liver disease (GALD) is a rare perinatal disorder characterized by intra- and extrahepatic iron overload. It is believed to result from complement-mediated liver injury, in which the classical complement pathway is activated by maternal antibody/fetal antigen complexes, leading to hepatocyte lysis by the membrane attack complex C5b9. According to some authors, C5b9 expression in more than 75% of liver parenchyma is specific for GALD.
We conducted a retrospective multicentric immunohistochemical study with anti-C5b9 in GALD cases (n = 25) and non-GALD cases with iron overload (n = 36) and without iron overload (n = 18).
C5b9 was expressed in 100% of GALD cases but involved more than 75% of the liver parenchyma in only 26% of the cases. C5b9 was detected in 26.75% of the non-GALD cases with more than 75% of positive parenchyma in maternal erythrocytic alloimmunization, herpes and enterovirus hepatitis, bile acid synthetic defect, DGUOK mutation, Gaucher disease, cystic fibrosis, and giant-cell hepatitis with autoimmune hemolytic anemia.
Diagnosis and therapeutic management of GALD cannot only be based on C5b9 expression in liver samples as it is not specific of this disease.
由妊娠同种免疫机制引起的新生儿血色素沉着症或妊娠同种免疫性肝病（GALD）是一种罕见的围产期疾病，其特征为肝内和肝外铁过载。据信它是由补体介导的肝损伤所致，其中经典补体途径被母体抗体/胎儿抗原复合物激活，导致膜攻击复合物C5b9介导肝细胞溶解。一些作者认为，肝实质中超过75%表达C5b9是GALD的特异性表现。
我们对GALD病例（n = 25）、有铁过载的非GALD病例（n = 36）和无铁过载的非GALD病例（n = 18）进行了一项回顾性多中心免疫组织化学研究，使用抗C5b9抗体。
100%的GALD病例中检测到C5b9表达，但仅26%的病例中C5b9累及超过75%的肝实质。在26.75%的非GALD病例中检测到C5b9，这些病例包括母体红细胞同种免疫、疱疹和肠道病毒肝炎、胆汁酸合成缺陷、DGUOK突变、戈谢病、囊性纤维化以及伴有自身免疫性溶血性贫血的巨细胞肝炎，且阳性实质超过75%。
GALD的诊断和治疗管理不能仅基于肝样本中C5b9的表达，因为它并非该疾病的特异性指标。
