The Japanese experience and pharmacokinetics of antenatal maternal high-dose immunoglobulin treatment as a prophylaxis for neonatal hemochromatosis in siblings

Okada, Noriki; Sasaki, Akira; Saito, Jumpei; Mitani, Yusuke; Yachie, Akihiro; Takahashi, Hironori; Matsubara, Shigeki; Tenkumo, Chiaki; Tanaka, Hirokazu; Hata, Toshiyuki; Motomura, Kenichiro; Nagasawa, Junko; Wada, Yuka; Sako, Mayumi; Yamaguchi, Koshi; Matsumoto, Kenji; Nakamura, Hidefumi; Sago, Haruhiko; Mizuta, Koichi

doi:10.1080/14767058.2018.1487940

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…2 Consistent with the alloim-mune mechanism, GALD exhibits high recurrence rates up to 90% in pregnancies that can be prevented by antenatal intravenous immunoglobulin (IVIG) treatment. 1,[3][4][5] In the present study, we reported two cases with GALD recurrence that was prevented by antenatal IVIG treatment in the second trimester.…”

supporting

confidence: 47%

“…The current treatment consists of antenatal IVIG (1 g•kg -1 ) administrations at 14, 16, 18 WG and contin-ued weekly to the end of pregnancy. 1,[3][4][5] It seems to be crucial to continue treatment until at least the 35 WG, for a total of 20 doses; whereas, the recommended dose is 60 g considering the side effects and the required infusion time. 1 It is important to note that in both of the presented cases, the treatment was initiated later than the recommended gestational week due to late admission to our clinic.…”

Section: Discussionmentioning

confidence: 99%

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Prevention of Gestational Alloimmune Liver Disease by Intravenous Immunoglobulin Administration in the Second Trimester: A Presentation of Two Cases

ALKAN BÜLBÜL,

KİRTİŞ,

KANDEMİR

et al. 2023

J Clin Obstet Gynecol

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Gestational alloimmune liver disease (GALD) is identified as a member of the maternal-fetal alloimmune diseases. The target of alloantibodies in GALD is fetal liver where specific antigen is believed to be expressed mainly in developing hepatocytes. The attack of alloantibodies causes activation of fetal complement causing a developmental failure of liver parenchyma resulting in replacement of hepatocyte progenitors with mature hepatocytes. The progenitorinduced profibrogenic signals lead to extensive parenchymal fibrosis. 1 Moreover, main phenotypic manifestation of GALD seems to be neonatal liver disease associated with hemosiderosis of various extra-hepatic tissues which is defined as neonatal hemochromatosis (NH). 2 Consistent with the alloim-mune mechanism, GALD exhibits high recurrence rates up to 90% in pregnancies that can be prevented by antenatal intravenous immunoglobulin (IVIG) treatment. 1,[3][4][5] In the present study, we reported two cases with GALD recurrence that was prevented by antenatal IVIG treatment in the second trimester. CASE REPORTS CASE 1A 30-year-old woman, gravida 3 para 1 with a history of GALD, applied for prenatal consultation at 24 week of gestation (WG). The index case was uncomplicated until 37 WG. However; at this time, oligohydramnios and fetal growth restriction were

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supporting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Prevention of Gestational Alloimmune Liver Disease by Intravenous Immunoglobulin Administration in the Second Trimester: A Presentation of Two Cases

ALKAN BÜLBÜL,

KİRTİŞ,

KANDEMİR

et al. 2023

J Clin Obstet Gynecol

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“…One child whose mother did not receive immunoglobulin treatment who underwent LDLT from the puerperal mother developed neonatal hemochromatosis. Antenatal maternal high-dose intravenous immunoglobulin treatment has been reported to be effective for preventing neonatal hemochromatosis recurrence [ 30 ]. In younger siblings of patients with OTCD, carbamoyl phosphate synthetase 1 deficiency, MMA, and Niemann-Pick disease type C, 4 of the mothers had prenatal amniocentesis.…”

Section: Discussionmentioning

confidence: 99%

Outcomes After Living Donor Liver Transplantation in Pediatric Patients with Inherited Metabolic Diseases

et al. 2021

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Background There is no consensus about the long-term prognosis of pediatric patients with a variety of rare liver diseases but with inherited metabolic diseases (IMDs). We retrospectively reviewed the developmental outcomes of patients with IMDs undergoing living donor liver transplantation (LDLT). Material/Methods Between May 2001 and December 2020, of 314 pediatric patients who underwent LDLT, 44 (14%) had IMDs. The median age at LDLT was 3.0 years old (range 0–15.0 years). Associations between the post-transplant complications and graft survival rate in patients with IMDs and biliary atresia (BA) were calculated. We evaluated the safety of LDLT from heterozygous carrier donors, the prognosis of patients with IMDs who have metabolic defects expressed in other organs, and developmental outcomes of patients with IMDs. Results The 10-year graft survival rates in patients with IMDs and BA were 87% and 94%, respectively ( P =0.041), and the causes of graft failure included pneumocystis pneumonia, acute lung failure, hemophagocytic syndrome, hepatic vein thrombosis, portal vein thrombosis, and sepsis. The rate of post-transplant cytomegalovirus viremia in patients with IMDs was higher than that of patients with BA ( P =0.039). Of 39 patients with IMDs, 15 patients (38%) had severe motor and intellectual disabilities in 4 patients, intellectual developmental disorders including epilepsy in 2, and attention-deficit hyperactivity disorder in 2. Of 28 patients with IMDs, 13 (46%) needed special education. Conclusions The long-term outcomes of LDLT in patients with IMDs are good. However, further long-term social and educational follow-up regarding intellectual developmental disorders is needed.

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“…Epidemiological data show that once a woman has given birth to a baby with GALD, there is approximately 80-95% risk that the subsequent babies will also suffer from GALD, even with another father [14][15][16]. Others have reported a recurrence rate of approximately 70% [17].…”

Section: Introductionmentioning

confidence: 99%

Hunting for the elusive target antigen in gestational alloimmune liver disease (GALD)

Rieneck,

Rasmussen,

Schoof

et al. 2023

PLoS ONE

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The prevailing concept is that gestational alloimmune liver disease (GALD) is caused by maternal antibodies targeting a currently unknown antigen on the liver of the fetus. This leads to deposition of complement on the fetal hepatocytes and death of the fetal hepatocytes and extensive liver injury. In many cases, the newborn dies. In subsequent pregnancies early treatment of the woman with intravenous immunoglobulin can be instituted, and the prognosis for the fetus will be excellent. Without treatment the prognosis can be severe. Crucial improvements of diagnosis require identification of the target antigen. For this identification, this work was based on two hypotheses: 1. The GALD antigen is exclusively expressed in the fetal liver during normal fetal life in all pregnancies; 2. The GALD antigen is an alloantigen expressed in the fetal liver with the woman being homozygous for the minor allele and the father being, most frequently, homozygous for the major allele. We used three different experimental approaches to identify the liver target antigen of maternal antibodies from women who had given birth to a baby with the clinical GALD diagnosis: 1. Immunoprecipitation of antigens from either a human liver cell line or human fetal livers by immunoprecipitation with maternal antibodies followed by mass spectrometry analysis of captured antigens; 2. Construction of a cDNA expression library from human fetal liver mRNA and screening about 1.3 million recombinants in Escherichia coli using antibodies from mothers of babies diagnosed with GALD; 3. Exome/genome sequencing of DNA from 26 presumably unrelated women who had previously given birth to a child with GALD with husband controls and supplementary HLA typing. In conclusion, using the three experimental approaches we did not identify the GALD target antigen and the exome/genome sequencing results did not support the hypothesis that the GALD antigen is an alloantigen, but the results do not yield basis for excluding that the antigen is exclusively expressed during fetal life., which is the hypothesis we favor.

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The Japanese experience and pharmacokinetics of antenatal maternal high-dose immunoglobulin treatment as a prophylaxis for neonatal hemochromatosis in siblings

Abstract: This treatment prevented the recurrence of NH in siblings in Japanese women. We examined the details of serum IgG concentrations and introduced a new pharmacokinetic simulation model of IgG concentrations during IVIG treatment.

Cited by 5 publications

References 25 publications

Prevention of Gestational Alloimmune Liver Disease by Intravenous Immunoglobulin Administration in the Second Trimester: A Presentation of Two Cases

Prevention of Gestational Alloimmune Liver Disease by Intravenous Immunoglobulin Administration in the Second Trimester: A Presentation of Two Cases

Outcomes After Living Donor Liver Transplantation in Pediatric Patients with Inherited Metabolic Diseases

Hunting for the elusive target antigen in gestational alloimmune liver disease (GALD)

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