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Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets

Cholangiopathies are defined as focal or extensive damage of the bile ducts. According to the pathogenetic mechanism, it may be immune-mediated or due to genetic, infectious, toxic, vascular, and obstructive causes. Their chronic evolution is characterized by inflammation, obstruction of bile flow,...

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Autores principales: Grama, Alina, Mititelu, Alexandra, Sîrbe, Claudia, Benţa, Gabriel, Pop, Tudor Lucian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623351/
https://www.ncbi.nlm.nih.gov/pubmed/37928553
http://dx.doi.org/10.3389/fimmu.2023.1206025
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author Grama, Alina
Mititelu, Alexandra
Sîrbe, Claudia
Benţa, Gabriel
Pop, Tudor Lucian
author_facet Grama, Alina
Mititelu, Alexandra
Sîrbe, Claudia
Benţa, Gabriel
Pop, Tudor Lucian
author_sort Grama, Alina
collection PubMed
description Cholangiopathies are defined as focal or extensive damage of the bile ducts. According to the pathogenetic mechanism, it may be immune-mediated or due to genetic, infectious, toxic, vascular, and obstructive causes. Their chronic evolution is characterized by inflammation, obstruction of bile flow, cholangiocyte proliferation, and progression toward fibrosis and cirrhosis. Immune-mediated cholangiopathies comprise primary sclerosing cholangitis (PSC), autoimmune cholangitis and IgG4-associated cholangitis in adults and biliary atresia (BA), neonatal sclerosing cholangitis (NSC) in children. The main purpose of this narrative review was to highlight the similarities and differences among immune-mediated cholangiopathies, especially those frequent in children in which cholangiocyte senescence plays a key role (BA, NSC, and PSC). These three entities have many similarities in terms of clinical and histopathological manifestations, and the distinction between them can be hard to achieve. In BA, bile duct destruction occurs due to aggression of the biliary cells due to viral infections or toxins during the intrauterine period or immediately after birth. The consequence is the activation of the immune system leading to severe inflammation and fibrosis of the extrahepatic biliary tract, lumen stenosis, and impairment of the biliary flow. PSC is characterized by inflammation and fibrosis of intra- and extrahepatic bile ducts, leading to secondary biliary cirrhosis. It is a multifactorial disease that occurs because of genetic predisposition [human leukocyte antigen (HLA) and non-HLA haplotypes], autoimmunity (cellular immune response, autoantibodies, association with inflammatory bowel disease), environmental factors (infections or toxic bile), and host factors (intestinal microbiota). NSC seems to be a distinct subgroup of childhood PSC that appears due to the interaction between genetic predisposition (HLA B8 and DR3) and the disruption of the immune system, validated by elevated IgG levels or specific antibodies [antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA)]. Currently, the exact mechanism of immune cholangiopathy is not fully understood, and further data are required to identify individuals at high risk of developing these conditions. A better understanding of the immune mechanisms and pathophysiology of BA, NSC, and PSC will open new perspectives for future treatments and better methods of preventing severe evolution.
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spelling pubmed-106233512023-11-04 Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets Grama, Alina Mititelu, Alexandra Sîrbe, Claudia Benţa, Gabriel Pop, Tudor Lucian Front Immunol Immunology Cholangiopathies are defined as focal or extensive damage of the bile ducts. According to the pathogenetic mechanism, it may be immune-mediated or due to genetic, infectious, toxic, vascular, and obstructive causes. Their chronic evolution is characterized by inflammation, obstruction of bile flow, cholangiocyte proliferation, and progression toward fibrosis and cirrhosis. Immune-mediated cholangiopathies comprise primary sclerosing cholangitis (PSC), autoimmune cholangitis and IgG4-associated cholangitis in adults and biliary atresia (BA), neonatal sclerosing cholangitis (NSC) in children. The main purpose of this narrative review was to highlight the similarities and differences among immune-mediated cholangiopathies, especially those frequent in children in which cholangiocyte senescence plays a key role (BA, NSC, and PSC). These three entities have many similarities in terms of clinical and histopathological manifestations, and the distinction between them can be hard to achieve. In BA, bile duct destruction occurs due to aggression of the biliary cells due to viral infections or toxins during the intrauterine period or immediately after birth. The consequence is the activation of the immune system leading to severe inflammation and fibrosis of the extrahepatic biliary tract, lumen stenosis, and impairment of the biliary flow. PSC is characterized by inflammation and fibrosis of intra- and extrahepatic bile ducts, leading to secondary biliary cirrhosis. It is a multifactorial disease that occurs because of genetic predisposition [human leukocyte antigen (HLA) and non-HLA haplotypes], autoimmunity (cellular immune response, autoantibodies, association with inflammatory bowel disease), environmental factors (infections or toxic bile), and host factors (intestinal microbiota). NSC seems to be a distinct subgroup of childhood PSC that appears due to the interaction between genetic predisposition (HLA B8 and DR3) and the disruption of the immune system, validated by elevated IgG levels or specific antibodies [antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA)]. Currently, the exact mechanism of immune cholangiopathy is not fully understood, and further data are required to identify individuals at high risk of developing these conditions. A better understanding of the immune mechanisms and pathophysiology of BA, NSC, and PSC will open new perspectives for future treatments and better methods of preventing severe evolution. Frontiers Media S.A. 2023-10-20 /pmc/articles/PMC10623351/ /pubmed/37928553 http://dx.doi.org/10.3389/fimmu.2023.1206025 Text en Copyright © 2023 Grama, Mititelu, Sîrbe, Benţa and Pop https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Grama, Alina
Mititelu, Alexandra
Sîrbe, Claudia
Benţa, Gabriel
Pop, Tudor Lucian
Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets
title Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets
title_full Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets
title_fullStr Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets
title_full_unstemmed Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets
title_short Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets
title_sort immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623351/
https://www.ncbi.nlm.nih.gov/pubmed/37928553
http://dx.doi.org/10.3389/fimmu.2023.1206025
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