Relevance of C5b9 immunostaining in the diagnosis of neonatal hemochromatosis

Dubruc, Estelle; Nadaud, Béatrice; Ruchelli, Eduardo D.; Heissat, Sophie; Baruteau, Julien; Broué, Pierre; Debray, Dominique; Cordier, Marie‐Pierre; Miossec, Pierre; Russo, Pierre; Collardeau‐Frachon, Sophie

doi:10.1038/pr.2017.8

Cited by 17 publications

(15 citation statements)

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“…Nonimmune complex-mediated complement activation may occur in this setting. Seventy-five percent staining for C5b-9 as a cutoff point for GALD was challenged by Dubruc et al 18 About a quarter of their non-GALD cases (n ¼ 36) had more than 75% positive parenchymal staining; on the other hand, only a quarter of GALD cases (n ¼ 25) showed more than 75% parenchymal staining. In the same study, 3 cases of liver disease without EHNRS also showed more than 75% parenchymal C5b-9 staining.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have focused on the utility of C5b-9 immunohistochemistry in the diagnosis of NH. 18 However, some centers, including tertiary academic hospitals, do not have standardized C5b-9 immunohistochemistry for clinical use. The need for this antibody often arises from the observation of hepatic and extrahepatic siderosis of hemochromatotic type, that is, the NH phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…17 Considering the plethora of causes of complement activation in the perinatal period, it is not surprising that a recent multi-institutional study from Europe challenged the specificity of C5b-9 immunohistochemistry in the diagnosis of GALD. 18 Distinguishing GALD from other causes of NH is important because IVIG can not only alleviate symptoms in index cases but also prevent/ alleviate GALD in future pregnancies. 13 In this study, we systematically evaluated both EHNRS and hepatic C5b-9 immune complex deposition in patients with perinatal liver failure in a large tertiary pediatric center.…”

Section: Introductionmentioning

confidence: 99%

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Extrahepatic Nonreticuloendothelial Siderosis Is Not Specific to Gestational Alloimmune Liver Disease

Ferguson

Castro

et al. 2019

Pediatr Dev Pathol

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Autopsy reports of 78 stillbirths and early infant deaths (up to age 8 weeks) were reviewed to investigate the prevalence of extrahepatic nonreticuloendothelial siderosis (EHNRS) in the context of neonatal liver failure. Of these, 10 liveborns (12.8%), M:F 3:2, with mean gestational age 37.6 weeks (range: 35–39) and mean age at the time of demise 19.1 days (range: 7–42), showed significant liver injury: infection (n = 7, viral > fungal), congenital malformations (n = 2), and ischemia (n = 1). None had maternal history of gestational alloimmune liver disease (GALD) or previous fetal/neonatal death due to liver failure. Seven of 10 cases (70%) showed EHNRS: pancreas (n = 6), kidneys (n = 4), thyroid and adrenal glands (n = 3), and bronchial glands and heart (n = 2). Iron deposition was most frequent in the pancreas (60%), most diffuse in the kidneys, and seen in at least 2 organs, with pancreas and kidney being the most frequent combination. Hepatic C5b-9 expression was variable (1+ to 4+) except 1 case (100% necrosis). The duration of illness and the mean age at the time of demise tended to be higher in those with EHNRS. In summary, hepatic and EHNRS, with or without C5b-9 expression, are not specific for GALD. Other causes of liver failure should be investigated as clinically and pathologically appropriate.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Extrahepatic Nonreticuloendothelial Siderosis Is Not Specific to Gestational Alloimmune Liver Disease

Ferguson

Castro

et al. 2019

Pediatr Dev Pathol

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“…A study of 44 cases with neonatal liver failure (22 NHs, and 22 non-NHs) that were found only six in the NH group were definite GALD if based on C5b-9 IHC ( 20 ). Dubruc et al reported C5b-9 that was expressed in 100% of GALD cases, yet also in 27% of non-GALD cases (enterovirus hepatitis, bile acid synthetic defect, DGUOK mutation, Gaucher disease, cystic fibrosis, and giant-cell hepatitis with autoimmune hemolytic anemia) ( 30 ). Regarding these controversial findings, a careful application and interpretation of the C5b-9 IHC are indispensable for an accurate diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Intravenous Immunoglobulin/Exchange Transfusion Therapy on Gestational Alloimmune Liver Disease

et al. 2021

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Background: Gestational alloimmune liver disease (GALD) is a rare but critical cause of neonatal liver failure. After discovering the maternal–fetal alloimmune mechanism, intravenous immunoglobulin (IVIG) with or without exchange transfusion (ET) has gradually replaced antioxidant cocktails as the first-line therapy. Whether such therapy changes the outcome of neonates with GALD is yet to be defined.Method: We reported a pair of twins with discordant presentations, mild and self-limited in the older, whereas liver failure in the younger, who was successfully rescued by ET and IVIG. To investigate the outcome after therapeutic alteration, 39 cases between 2005 and 2020 from literature research were collected.Results: Half of the collected cases (47.1%) were preterm. Common presentations were ascites, jaundice, respiratory distress, hepatomegaly, and edema. Leading laboratory abnormalities were coagulopathy, hypoalbuminemia, and elevated serum ferritin. Salivary gland biopsy and magnetic resonance imaging detected extrahepatic siderosis in 70% (14/20) and 56% (14/25), respectively. IVIG, ET, and liver transplantation were performed in 19 (48.7%), 15 (38.5%), and 8 (20.5%) patients, respectively. The overall survival (OS) rate and native liver survival (NLS) rate were 64.1% (25/39) and 43.6% (17/39), respectively. Although the compiled results did not support a significant benefit, the OS and NLS were higher in the IVIG with/without ET group compared with those treated with conventional therapy [OS (70 vs. 57.9%) and NLS (55 vs. 31.6%), respectively].Conclusion: A high index of suspicion for GALD is crucial when facing a neonate with liver failure. Despite no significant influence on the outcome over conventional therapy in such a rare and detrimental disease, IVIG with or without ET can be worth trying before resorting to liver transplantation, which is resource-demanding and technique-challenging in small infants.

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“…Son positivos a la tinción inmunohistoquímica C5b-9; esto no es específico de GALD; sin embargo, se ha demostrado asociación cuando se observa en más del 75% de la muestra. 19,20 Los canalículos biliares se describen con tapones biliares y los conductos portales relativamente intactos o, bien, con pocos datos de inflamación. El proceso de inflamación puede verse como infiltración de macrófagos y neutrófilos.…”

Section: Diagnósticounclassified

Actualización en la hemocromatosis neonatal

Garin

Mondragón

2021

Acta Pediatr Mex

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La insuficiencia hepática durante el periodo neonatal tiene una mortalidad que alcanza, incluso, el 24%. Su causa puede ser infecciosa, metabólica, por isquemia o por hemocromatosis neonatal. Es de origen autoinmunitario hasta en un 80 a 90% y se conoce como enfermedad hepática autoinmunitaria gestacional. Se produce por el paso transplacentario de inmunoglobulinas maternas IgG a partir de las 12 semanas de gestación dirigidas contra receptores hepáticos neonatales. Causa un daño hepático grave acompañado de un depósito de hierro en el hígado y en otros tejidos, como las glándulas salivales o la tiroides, con lo que se establece el diagnóstico mediante biopsia o resonancia magnética. El tratamiento oportuno reduce su mortalidad del 80 al 20% y es mediante la administración de gammaglobulina a 1 mg/kg/dosis.PALABRAS CLAVE: Hemocromatosis neonatal; insuficiencia hepática; cirrosis hepática; enfermedad hepática; glándula tiroides; biopsia; gammaglobulina; hierro.

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Relevance of C5b9 immunostaining in the diagnosis of neonatal hemochromatosis

Abstract: Diagnosis and therapeutic management of GALD cannot only be based on C5b9 expression in liver samples as it is not specific of this disease.

Cited by 17 publications

References 75 publications

Extrahepatic Nonreticuloendothelial Siderosis Is Not Specific to Gestational Alloimmune Liver Disease

Extrahepatic Nonreticuloendothelial Siderosis Is Not Specific to Gestational Alloimmune Liver Disease

Efficacy of Intravenous Immunoglobulin/Exchange Transfusion Therapy on Gestational Alloimmune Liver Disease

Actualización en la hemocromatosis neonatal

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