Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody–positive versus antimitochondrial autoantibody–negative primary biliary cirrhosis
Open accessAbstract
Substantial evidence supports dysregulated B-cell immune responses in patients with primary biliary cirrhosis (PBC), including the presence of serum antimitochondrial antibodies (AMAs). However, recent reports from murine models of PBC suggest that B cells may also provide regulatory function, and indeed the absence of B cells in such models leads to exacerbation of disease. The vast majority of patients with PBC have readily detectable AMAs, but a minority (<5%) are AMA negative (AMA−), even with recombinant diagnostic technology. This issue prompted us to examine the nature of B-cell infiltrates surrounding the portal areas in AMA-positive (AMA+) and AMA− patients, because they display indistinguishable clinical features. Of importance was the finding that the degree of bile duct damage around the portal areas was significantly milder in AMA+ PBC than those observed in AMA− PBC patients. The portal areas from AMA− patients had a significant increase of cluster of differentiation (CD)5+ cells infiltrating the ductal regions, and the levels of B-cell infiltrates were worse in the early phase of bile duct damage. The frequency of positive portal areas and the magnitude of CD5+ and CD20+ cellular infiltrates within areas of ductal invasion is associated with the first evidence of damage of biliary duct epithelia, but becomes reduced in the ductopenia stage, with the exception of CD5+ cells, which remain sustained and predominate over CD20+ cells. Conclusion: Our data suggest a putative role of B-cell autoimmunity in regulating the portal destruction characteristic of PBC. (Hepatology 2012)
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Histologically, AMA-negative PBC shows greater bile duct damage and loss than AMA-positive PBC.
“Histologically, AMA-negative PBC has been shown to have greater bile duct damage and loss compared with AMA-positive PBC.(117)(118)”
From Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases (2019) · cites this paper as [118]
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- Authors
- Jin, Q., Moritoki, Y., Lleo, A., Tsuneyama, K., Invernizzi, P., Moritoki, H., Kikuchi, K., Lian, Z.-X., Hirschfield, G. M., Ansari, A. A., Coppel, R. L., Gershwin, E. M., & Niu, J.
- Affiliations
- First Hospital of Jilin University (CN)
- Akita University (JP)
- University of Toyama (JP)
- IRCCS Humanitas Research Hospital (IT)
- Teikyo University Hospital, Mizonokuchi (JP)
- University of Science and Technology of China (CN)
- University of Toronto (CA)
- Emory University (US)
- Monash University (AU)
- University of California, Davis (US)
- Corresponding author
- Gershwin, Eric M.
- ORCID
- Venue
- Hepatology
- Published
- 2012-05
- Volume
- 55
- Issue
- 5
- Pages
- 1495-1506
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC3299932
- OpenAlex
- W1977408655
- Cited by
- 37
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 6 · 2022: 3 · 2021: 2 · 2019: 1 · 2018: 3 · 2017: 4 · 2015: 1 · 2014: 6 · 2013: 5 · 2012: 4
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- National Natural Science Foundation of China (30972610, 200705128, 30771912, 2008ZX10002-004, 20073531)
- People's Government of Jilin Province
- National Institutes of Health (DK 39588)
- Japan Society for the Promotion of Science (21590433, 22890024)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 39588, R37DK039588, R01DK039588)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Rheumatology › IgG4-Related and Inflammatory Diseases
- Keywords
- primary biliary cirrhosis, antimitochondrial antibodies, B-cell infiltrates, CD5+ B cells, CD20+ B cells, bile duct injury, portal inflammation, B cell-mediated autoimmunity, regulatory B cells, ductopenia, biliary epithelium
- MeSH terms
- Adult, Aged, Autoantibodies, Bile Ducts, Biopsy, Needle, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunohistochemistry, Liver Cirrhosis, Biliary, Male, Middle Aged, Mitochondria, Liver, Severity of Illness Index, Confidence Intervals, Case-Control Studies, Statistics, Nonparametric, Antigens, CD20, Hepatitis C, Chronic
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