Antimitochondrial Antibodies (cont.)
John M. Vierling, MD, FACP
John M. Vierling M.D. is Professor of Medicine and Surgery at the Baylor College of Medicine in Houston, Texas, where he also serves as Director of Baylor Liver Health and Chief of Hepatology. In addition, he is the Director of Advanced Liver Therapies, a center devoted to clinical research in hepatobiliary diseases at St. Luke's Episcopal Hospital. Dr. Vierling is board certified in internal medicine and gastroenterology and a Fellow of the American College of Physicians.
Leslie J. Schoenfield, MD, PhD
Dr. Schoenfield served as associate professor of medicine and consultant in gastroenterology on the faculty of the Mayo Clinic for seven years. He became a professor of medicine in residence at UCLA from 1972 to 1999 (now emeritus). He was the director of gastroenterology at Cedars-Sinai Medical Center in Los Angeles for 25 years, where he received the chief resident's teaching award, the president's award, and the pioneer of medicine award.
In this Article
- What are antimitochondrial antibodies (AMA)?
- Do AMA cause the destruction of the bile ducts in PBC?
- How is the blood test for AMA done?
- What is the value of the AMA blood test?
Do AMA cause the destruction of the bile ducts in PBC?
In as much as the bile ducts are the main targets of destruction in PBC, the
question was asked whether the AMA reacts with the epithelial cells that line
the bile ducts. So, investigators prepared antibodies to PDC-E2. As expected,
they found that these antibodies bound to the mitochondria within the cells.
But, sure enough, recent information suggests that these AMA autoantibodies also
bind to PDC-E2 that lies outside the mitochondria, yet within the epithelial
cells lining the bile ducts.
This accumulation of PDC-E2 within the biliary epithelial cells is observed exclusively in the livers of patients with PBC, and not in normal livers or in livers from patients with any other types of liver disease. Interestingly, it was also observed in the livers of those two to five percent of PBC patients who do not have AMA in their blood (AMA-negative PBC). Furthermore, intense binding of these antibodies to biliary epithelial cells was also found to be the earliest indication of recurrence of PBC in a transplanted liver. (PBC is sometimes treated by liver transplantation.)
Nevertheless, no evidence exists that the AMA itself causes the destruction of the biliary epithelial cells lining the small bile ducts. Neither the presence nor the amount (titer) of AMA in the blood appears to be related to the inflammatory destruction of the bile ducts. Indeed, immunization of animals with PDC-E2 antigen results in production of AMA without any liver or bile duct damage (pathology).
How is the blood test for AMA done?
The most economical test for AMA applies diluted samples of a
patient's serum onto tissue sections from rat stomach or kidney in the
laboratory. (Remember that mitochondria are present in all cells, not just the cells of
the liver and bile ducts.) Serum antibodies that attach (bind) to mitochondrial
membranes within the tissue cells can then be observed with a microscope. The
most dilute sample of serum showing this binding reaction is reported, using the
term titer. The titer indicates the most dilute serum sample that reacts with
the tissue mitochondria. A higher titer means there is a greater amount of AMA
in the serum.
The antigen recognized by AMA in patients with PBC is now known to be PDC-E2 and is also often referred to as the M2 antigen. So, newly developed tests for antibodies that bind to PDC-E2 are more specific and are now available to confirm the diagnosis of PBC.
http://www.medicinenet.com/antimitochondrial_antibodies/article.htm
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