Primary Biliary Cirrhosis (cont.)
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What is the role of infection?
The possibility that PBC is caused by an infection with a virus, bacterium,
or fungus has generated a number of studies. To date, none has shown
conclusively that PBC is an infectious disease or even that it is triggered by a
self-limited (nonpersistent) infection. Clearly, PBC is not associated with
infection by any of the known hepatitis viruses. Furthermore, none of the new
viruses that may cause liver diseases have been found preferentially or
exclusively in patients with PBC.
Investigators are currently pursuing leads suggesting that the biliary
epithelial cells of patients with PBC may contain an infectious virus that
belongs to the class of viruses called retroviruses. (The human immunodeficiency
virus, HIV, is an example of a retrovirus.) These studies have identified
genetic fragments of a retrovirus in the biliary epithelial cells of patients
with PBC. Nevertheless, further research is required to answer the important
question of whether PBC is caused by a retroviral infection.
The possibility that PBC is caused by infection with bacteria has intrigued
clinical investigators for decades. You see, the mitochondria in the cells of
mammals were derived, during evolution, from bacteria. Thus, many bacteria
contain antigens that react with the AMA found in patients with PBC. Some of
these bacteria have been cultured from the urine of patients with PBC who have
recurrent urinary tract infections. Interestingly enough, as discussed later,
recurrent urinary tract infection has been recognized as a risk factor for
developing PBC.
This association between urinary tract infection and PBC led to the
speculation that a bacterial infection might trigger an immune response that
developed into an autoimmune reaction. Although this speculation is plausible,
there is currently no direct evidence that this sequence of events occurs in
PBC. As a matter of fact, molecular techniques now exist to screen livers for
the presence of any type of bacteria. So far, these kinds of studies have found
no evidence of a chronic bacterial infection in PBC.
Another intriguing possibility is that an infection with a virus, bacterium,
fungus or parasite might introduce foreign proteins that mimic the protein
antigens of mitochondria. An immune response against these foreign proteins
could develop antibodies and T lymphocytes that react with the mimicked
self-proteins, thereby resulting in autoimmunity. In other words, the body's
immune system responds to the foreign proteins but it reacts against its own
mitochondrial proteins. This phenomenon is called molecular mimicry.
One of the best examples of molecular mimicry is found in rheumatic fever.
This condition is an autoimmune reaction involving the skin, joints, and heart
muscle, that is caused by an immune response to a streptococcal bacterial
infection. Now, rheumatic fever is usually diagnosed within a few weeks of
having strep throat. Physicians, therefore, recognized the relationship between
the two events (streptococcal infection and rheumatic fever) before molecular
mimicry was understood. PBC, however, is usually a more subtle condition that
might not be diagnosed for many years. Therefore, if a transient infection were
to trigger molecular mimicry in PBC, causing an autoimmune reaction, the
relationship between the infection and the autoimmune disease might be easily
missed.
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