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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2020
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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. |
format | Online Article Text |
id | pubmed-7336326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
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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