A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis
Open accessAbstract
The antimitochondrial response in primary biliary cirrhosis (PBC) is the most highly directed and specific self-reacting antibody in human immunopathology. Originally, antimitochondrial antibodies (AMAs) were detected by indirect immunofluorescence (IIF) and found in approximately 90% of well-documented patients with PBC. The introduction of recombinant autoantigens and the use of immunoblotting have increased the sensitivity and specificity of AMAs, and they are now considered positive in approximately 95% of patients with PBC. Clearly, accurate autoantibody detection represents one of the fundamental requirements for reliable diagnostics in autoimmunity. To address the 5% of AMA-negative patients with PBC, we have generated and validated a bead assay for the detection of AMA. We enrolled 120 patients with PBC, including a non-random group of 30 rigorously proven AMA-negative patients, 50 healthy subjects, and 74 controls with autoimmune diseases (18 with primary sclerosing cholangitis, 16 with autoimmune hepatitis, and 40 with systemic lupus erythematosus). Individual bead assays were done with the three mitochondrial autoantigens, PDC-E2, BCOADC-E2, and OGDC-E2. As expected, 90 of 90 previously known AMA-positive patients remained positive with this assay but, interestingly, 20% of the rigorously defined AMA-negative patient group had antibodies to one or more of the mitochondrial autoantigens. Furthermore, 100% of these newly detected AMA-positive patients were anti-nuclear antibody (ANA) positive. Conclusion: The development of this assay reflects the potential for automated detection with rapid and reliable assaying and further highlights the diminished number of truly AMA-negative PBC patients. (Hepatology 2007;45:659–665.)
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Approximately 5% of patients with PBC are negative for AMA (or anti PDC-E2/M2 by ELISA).
“Approximately 5% of patients with PBC are negative for AMA (or anti PDC-E2/M2 by ELISA), although this figure in practice reflects the assays employed.263 264”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [263]
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- Authors
- Oertelt, S., Rieger, R., Selmi, C., Invernizzi, P., Ansari, A. A., Coppel, R. L., Podda, M., Leung, P. S. C., & Gershwin, E. M.
- Affiliations
- University of California, Davis (US)
- University of Milan (IT)
- Emory University (US)
- Monash University (AU)
- Corresponding author
- Gershwin, Eric M.
- Venue
- Hepatology
- Published
- 2007-03
- Volume
- 45
- Issue
- 3
- Pages
- 659-665
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2072206894
- Cited by
- 168
- References
- 1
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 12 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 9 · 2012: 13
- FWCI
- 11.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PUB – Publications at Bielefeld University (Bielefeld University) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (other-oa)
- Funders
- National Institutes of Health (n01dk092310-000, DK 39588)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 39588, DK-92310)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Autoimmune Bullous Skin Diseases
- Keywords
- antimitochondrial antibodies, primary biliary cirrhosis, mitochondrial autoantigens, PDC-E2, antinuclear antibodies, autoantibody detection, diagnostic sensitivity
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antibodies, Anti-Idiotypic, Antibody Specificity, Autoantigens, Cell Separation, Female, Humans, Immunoassay, Liver Cirrhosis, Biliary, Male, Microspheres, Middle Aged, Mitochondria, Liver, Case-Control Studies
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