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Review of primary sclerosing cholangitis with increased IgG4 levels

Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease. Sub-types of PSC have been described, most recently PSC with elevated serum and/or tissue IgG4 subclass. We aim to summarise the clinical phenotype, disease associations, differential diagnosis, response to therapy and path...

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Autores principales: Manganis, Charis D, Chapman, Roger W, Culver, Emma L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336326/
https://www.ncbi.nlm.nih.gov/pubmed/32684731
http://dx.doi.org/10.3748/wjg.v26.i23.3126
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author Manganis, Charis D
Chapman, Roger W
Culver, Emma L
author_facet Manganis, Charis D
Chapman, Roger W
Culver, Emma L
author_sort Manganis, Charis D
collection PubMed
description Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease. Sub-types of PSC have been described, most recently PSC with elevated serum and/or tissue IgG4 subclass. We aim to summarise the clinical phenotype, disease associations, differential diagnosis, response to therapy and pathogenic mechanisms underlying PSC-high IgG4 subtype. We reviewed PubMed, MEDLINE and Embase with the search terms “primary sclerosing cholangitis”, “IgG4”, and “IgG4-related sclerosing cholangitis (IgG4-SC)”. Elevated serum IgG4 are found in up-to one-quarter, and abundant IgG4-plasma cell infiltrates in the liver and bile ducts are found in up-to one-fifth of PSC patients. This group have a distinct clinical phenotype, with some studies reporting a more aggressive course of liver and associated inflammatory bowel disease, compared to PSC-normal IgG4 and the disease mimic IgG4-SC. Distinguishing PSC-high IgG4 from IgG4-SC remains challenging, requiring careful assessment of clinical features, organ involvement and tissue morphology. Calculation of serum IgG(4):IgG(1) ratios and use of a novel IgG(4):IgG RNA ratio have been reported to have excellent specificity to distinguish IgG4-SC and PSC-high IgG4 but require validation in larger cohorts. A role for corticosteroid therapy in PSC-high IgG4 remains unanswered, with concerns of increased toxicity and lack of outcome data. The immunological drivers underlying prominent IgG4 antibodies in PSC are incompletely defined. An association with PSC-high IgG4 and HLA class-II haplotypes (B*07, DRB1*15), T-helper2 and T-regulatory cytokines (IL4, IL10, IL13) and chemokines (CCL1, CCR8) have been described. PSC-high IgG4 have a distinct clinical phenotype and need careful discrimination from IgG4-SC, although response to immunosuppressive treatments and long-term outcome remains unresolved. The presence of IgG4 likely represents chronic activation to persistent antigenic exposure in genetically predisposed individuals.
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spelling pubmed-73363262020-07-16 Review of primary sclerosing cholangitis with increased IgG4 levels Manganis, Charis D Chapman, Roger W Culver, Emma L World J Gastroenterol Review Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease. Sub-types of PSC have been described, most recently PSC with elevated serum and/or tissue IgG4 subclass. We aim to summarise the clinical phenotype, disease associations, differential diagnosis, response to therapy and pathogenic mechanisms underlying PSC-high IgG4 subtype. We reviewed PubMed, MEDLINE and Embase with the search terms “primary sclerosing cholangitis”, “IgG4”, and “IgG4-related sclerosing cholangitis (IgG4-SC)”. Elevated serum IgG4 are found in up-to one-quarter, and abundant IgG4-plasma cell infiltrates in the liver and bile ducts are found in up-to one-fifth of PSC patients. This group have a distinct clinical phenotype, with some studies reporting a more aggressive course of liver and associated inflammatory bowel disease, compared to PSC-normal IgG4 and the disease mimic IgG4-SC. Distinguishing PSC-high IgG4 from IgG4-SC remains challenging, requiring careful assessment of clinical features, organ involvement and tissue morphology. Calculation of serum IgG(4):IgG(1) ratios and use of a novel IgG(4):IgG RNA ratio have been reported to have excellent specificity to distinguish IgG4-SC and PSC-high IgG4 but require validation in larger cohorts. A role for corticosteroid therapy in PSC-high IgG4 remains unanswered, with concerns of increased toxicity and lack of outcome data. The immunological drivers underlying prominent IgG4 antibodies in PSC are incompletely defined. An association with PSC-high IgG4 and HLA class-II haplotypes (B*07, DRB1*15), T-helper2 and T-regulatory cytokines (IL4, IL10, IL13) and chemokines (CCL1, CCR8) have been described. PSC-high IgG4 have a distinct clinical phenotype and need careful discrimination from IgG4-SC, although response to immunosuppressive treatments and long-term outcome remains unresolved. The presence of IgG4 likely represents chronic activation to persistent antigenic exposure in genetically predisposed individuals. Baishideng Publishing Group Inc 2020-06-21 2020-06-21 /pmc/articles/PMC7336326/ /pubmed/32684731 http://dx.doi.org/10.3748/wjg.v26.i23.3126 Text en ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Review
Manganis, Charis D
Chapman, Roger W
Culver, Emma L
Review of primary sclerosing cholangitis with increased IgG4 levels
title Review of primary sclerosing cholangitis with increased IgG4 levels
title_full Review of primary sclerosing cholangitis with increased IgG4 levels
title_fullStr Review of primary sclerosing cholangitis with increased IgG4 levels
title_full_unstemmed Review of primary sclerosing cholangitis with increased IgG4 levels
title_short Review of primary sclerosing cholangitis with increased IgG4 levels
title_sort review of primary sclerosing cholangitis with increased igg4 levels
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336326/
https://www.ncbi.nlm.nih.gov/pubmed/32684731
http://dx.doi.org/10.3748/wjg.v26.i23.3126
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