Antimitochondrial Antibodies (cont.)

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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.

Medically Reviewed by a Doctor on 2/21/2014

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