Hunting for the elusive target antigen in gestational alloimmune liver disease (GALD)
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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.
Originalsprog | Engelsk |
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Artikelnummer | e0286432 |
Tidsskrift | PLoS ONE |
Vol/bind | 18 |
Udgave nummer | 10 |
Antal sider | 25 |
ISSN | 1932-6203 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
Funding: (MHD), grant number 10-002161, Aase og Ejnar Danielsen’s foundation https:// danielsensfond.dk. (MHD), no grant number but application date is 05102018, Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis’ Legat (https:// www.legatbogen.dk/lge-sofus-carl-emil-friis-oghustru-olga-doris-friis-legat). (MHD), grant no 9039-00122B, The Independent Research Foundation of Denmark, https://dff.dk/en. (MHD), grant no NNF14CC0001, The Novo Nordisk Foundation, https://novonordiskfonden.dk. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2023 Rieneck et al.
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