A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis

Sabine Oertelt, Roman Rieger, Carlo Selmi, Pietro Invernizzi, Aftab A. Ansari, Ross L. Coppel, Mauro Podda, Patrick S C Leung, M. Eric Gershwin

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Abstract

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.

Original languageEnglish
Pages (from-to)659-665
Number of pages7
JournalHepatology
Volume45
Issue number3
DOIs
Publication statusPublished - Mar 2007

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ASJC Scopus subject areas

  • Hepatology

Cite this

Oertelt, S., Rieger, R., Selmi, C., Invernizzi, P., Ansari, A. A., Coppel, R. L., Podda, M., Leung, P. S. C., & Gershwin, M. E. (2007). A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis. Hepatology, 45(3), 659-665. https://doi.org/10.1002/hep.21583