Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis
Open accessAbstract
Background: Antinuclear antibodies (ANA) giving a rim-like/membranous (RL/M) or a multiple nuclear dot (MND) pattern are highly specific for primary biliary cirrhosis (PBC). Aim and subjects: To assess the prevalence of PBC specific ANAs, their Ig isotype, and their clinical significance in 90 PBC patients from Greece and Spain. Twenty eight patients with chronic hepatitis C, 23 patients with systemic lupus erythematosus, and 17 healthy subjects were studied as controls. Methods: PBC specific ANA reactivity was tested by indirect immunofluorescence using HEp2 cells as substrate and individual Ig class (IgG, IgA, IgM) and IgG subclass (IgG1, IgG2, IgG3, IgG4) specific antisera as revealing reagents. Results: Fourteen of 90 (15.6%) PBC patients had PBC specific ANA reactivity when an anti-IgG (total) antiserum was used as the revealing reagent while 58 (64.4%) were positive when specific antisera to each of the four IgG isotypes were used. The prevailing isotype was IgG3 for MND and IgG1 for RL/M. PBC patients with specific ANA, in particular of the IgG3 isotype, had significantly more severe biochemical and histological disease compared with those who were seronegative. None of the controls was positive. Conclusions: Disease specific ANA are present in the majority of patients with PBC when investigated at the level of immunoglobulin isotype. PBC specific ANA, in particular of the IgG3 isotype, are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.
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PBC-specific ANA against gp210 and sp100 are seen more often in severe PBC and may predict an unfavorable course independent of serum bilirubin.
“PBC-specific ANA (antibodies against gp210 and sp100 antigens) are more frequently observed in patients with severe PBC and their presence may also be predictive of an unfavourable course, irrespective of serum bilirubin [75][76][77]63,78].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [76]
The Results and Discussion (page not available in our copy) associate PBC-specific ANA with more severe disease and worse outcomes, particularly for the multiple-nuclear-dot pattern. The study tested immunofluorescence patterns rather than separately establishing these findings for anti-gp210 and anti-sp100, and it does not show that the outcome association is independent of serum bilirubin. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPBC-specific ANA against gp210 and sp100 are more frequently observed in severe PBC and may predict an unfavourable course irrespective of serum bilirubin.
“PBC-specific ANA (antibodies against gp210 and sp100 antigens) are more frequently observed in patients with severe PBC and their presence may also be predictive of an unfavourable course, irrespective of serum bilirubin [75][76][77]63,78].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [76]
The Results and Discussion (page unavailable) associate PBC-specific ANA staining patterns with more advanced disease and, particularly for multiple nuclear dot reactivity, worse outcomes. The study tested staining patterns rather than establishing these findings specifically for antibodies against both gp210 and sp100; although Table 1 reports bilirubin levels, the paper does not show that the outcome association is independent of serum bilirubin. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThere is evidence to suggest that PBC-linked ANA (in particular anti-gp210/anti-nuclear rim antibody) may be associated with more rapidly progressive disease and disease which is less responsive to UDCA therapy.
“There is evidence to suggest that PBC-linked ANA (in particular anti-gp210/anti-nuclear rim antibody) may be associated with more rapidly progressive disease and disease which is less responsive to UDCA therapy.76 79–82”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [82]
The Results (page unavailable) associate PBC-specific ANA, including rim-like/membranous reactivity, with more severe histological disease; the Discussion (page unavailable) also reports studies linking anti-gp210 to worse prognosis. These findings support the suggestion of a more severe disease course, but this paper does not establish faster progression or reduced responsiveness to UDCA. Its Results say only that IgG3-ANA-positive patients were more frequently receiving UDCA. (LLM, conf=0.88)
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- Authors
- Rigopoulou, E. I., Davies, E. T., Pares, A., Zachou, K., Liaskos, C., Bogdanos, D.-P., Rodes, J., Dalekos, G. N., & Vergani, D.
- Affiliations
- King's College Hospital (GB)
- University of Thessaly (GR)
- King's College London (GB)
- Corresponding author
- Vergani, D
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2005-03-07
- Volume
- 54
- Issue
- 4
- Pages
- 528-532
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC1774444
- OpenAlex
- W2065347776
- Cited by
- 134
- References
- 46
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 5 · 2013: 8 · 2012: 21
- FWCI
- 5.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion)
- University of Thessaly Institutional Repository (University of Thessaly) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Children's Liver Disease Foundation
- Instituto de Salud Carlos III (C03/02)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Keywords
- primary biliary cirrhosis, antinuclear antibodies, IgG isotypes, IgG3, IgG1, disease severity, chronic hepatitis C, systemic lupus erythematosus, autoantibody prevalence
- MeSH terms
- Adult, Aged, Antibodies, Antinuclear, Female, Humans, Immunoglobulin G, Immunoglobulin Isotypes, Liver Cirrhosis, Biliary, Lupus Erythematosus, Systemic, Male, Middle Aged, Prognosis, Severity of Illness Index, Biomarkers, Fluorescent Antibody Technique, Indirect, Hepatitis C, Chronic
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