Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis
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This study reports on a group of 20 patients with an initial diagnosis of primary biliary cirrhosis (PBC) whose serum tested negative for antimitochondrial antibodies by immunofluorescence. All had a clinical history compatible with primary biliary cirrhosis, and results of biochemical, histological, and radiological investigations were consistent with this diagnosis despite the absence of antimitochondrial antibodies by immunofluorescence. For comparison, these patients were matched for sex and serum bilirubin with 20 antimitochondrial antibody positive (> 1:160) and histologically confirmed primary biliary cirrhosis patients who served as controls. Serum samples from both groups were retested blindly for antimitochondrial antibodies using immunoblotting and for antibodies to the major M2 mitochondrial autoantigens by enzyme linked immunosorbent assay (ELISA). Three antimitochondrial antibody immunofluorescence negative patients had antimitochondrial antibodies by immunoblotting and ELISA; the remaining 17 patients were confirmed negative by all methods. The antimitochondrial antibody immunofluorescence positive controls were verified by immunoblotting or ELISA, or both. All 17 patients negative for antimitochondrial antibodies had antinuclear antibodies, often in high titres, compared with 3/17 of the antimitochondrial antibody positive controls (p = 0.0001). Additionally, the antimitochondrial antibody negative group also had significantly higher smooth muscle antibody titres (p = 0.03) and lower serum IgM (p = 0.01) and aspartate aminotransferase (p = 0.03) activities than the antimitochondrial antibody positive controls. Analysis of clinical findings, histological tests, serum bilirubin, alkaline phosphatase, alanine aminotransferase, and IgG, disclosed no significant differences between the two groups. This paper describes a group of patients with the clinical and histological features of PBC but who do not fulfil the usual criteria necessary to make this diagnosis. Because they also have very high titres of antinuclear antibodies, smooth muscle antibodies, and comparatively low IgM and aspartate aminotransferase activities, we believe they are distinct from PBC and have a syndrome of autoimmune cholangitis.
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Compared with AMA-positive PBC, AMA-negative PBC has higher prevalence of antinuclear and anti-smooth muscle antibodies and lower serum IgM levels.
“Although AMA-negative PBC patients are nearly identical to AMA-positive PBC patients, minor differences have been noted, including a higher prevalence of antinuclear and anti-smooth muscle antibodies and lower serum IgM levels.(111)(112)(113)”
From Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases (2019) · cites this paper as [112]
Compared with AMA-positive PBC, AMA-negative PBC has higher prevalence of antinuclear and anti-smooth muscle antibodies and lower serum IgM levels.
“Although AMA-negative PBC patients are nearly identical to AMA-positive PBC patients, minor differences have been noted, including a higher prevalence of antinuclear and anti-smooth muscle antibodies and lower serum IgM levels.(111)(112)(113)”
From Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases (2019) · cites this paper as [111]
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- Authors
- Michieletti, P., Wanless, I. R., Katz, A., Scheuer, P. J., Yeaman, S. J., Bassendine, M. F., Palmer, J. M., & Heathcote, E. J.
- Affiliations
- Newcastle University (GB)
- Venue
- Gut
- Publisher
- BMJ
- Published
- 1994-02
- Volume
- 35
- Issue
- 2
- Pages
- 260-265
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC1374505
- OpenAlex
- W2083293854
- Cited by
- 236
- References
- 36
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 4 · 2021: 3 · 2020: 2 · 2018: 2 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 3 · 2013: 2 · 2012: 5
- FWCI
- 9.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Rheumatology › IgG4-Related and Inflammatory Diseases
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Keywords
- primary biliary cirrhosis, autoimmune cholangitis, antinuclear antibodies, smooth muscle antibodies, immunofluorescence assay, Western blot, IgM, aspartate aminotransferase, differential diagnosis
- MeSH terms
- Adult, Aged, Autoantibodies, Autoimmune Diseases, Bile Ducts, Cholangitis, Female, Fluorescent Antibody Technique, Humans, Liver Cirrhosis, Biliary, Male, Middle Aged, Mitochondria, Liver
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