Primary Biliary Cirrhosis, Basics 2: Triggered Self-Destruction & the Loss of Self-Tolerance

At the end of this post you’ll find lengthy quotations, exiled there because I found myself not writing a blog but a review paper. I want to resist that habit.

You are your own worst enemy

I’ve heard that before, lots of times. And now it appears to be true.

In primary biliary cirrhosis (PBC), the cells lining the bile ducts that allow bile to leave the liver are destroyed, so the bile backs up and this accumulation damages liver cells and cirrhosis occurs. And what is attacking these bile ducts? My own immune system: hence, auto-immune.

What’s an autoimmune disease? has a succinct definition:

They are caused by the body’s own immune system getting confused and wrongly attacking the body’s good cells. . . .the immune system itself gets tricked into killing good normal cells. The immune system wrongly makes antibodies to normal cells, which cause these cells to be attacked and killed, just as if they were recognized as unhealthy virus-infected cells.

As if this weren’t bad enough, there is a second theory, that of the

Apoptosis error: cells commit suicide for some aberrant reason, and the immune system is only there to clean up afterward.

In spite of my desire to disassociate PBC from the stigma attached to the word cirrhosis, in an odd way primary biliary and alcoholic cirrhosis have something in common. Both are illnesses of self-destruction. But the difference is that the self-destruction of the alcoholic is one that the self can summon the will to inhibit. Not so with an auto-immune illness.

Some time I need to look for studies of the psychological reaction to auto-immune illness (I’m sure someone somewhere is working on this).

Putting it medically, my immune system is attacking my bile ducts. Putting it metaphorically, I am attacking myself.

OK, I know,  it is my cells attacking my body. You can call my metaphor anthropomorphism on the cellular level, but you can’t deny that I am my cells, I am my body.

I may be more than this, but if my self has no body to inhabit, although my soul or spirit may survive,  this self  — my self –won’t.

And that is hard to get my head around.  Am I so incompetent that my immune system can’t tell what’s normal and what isn’t?

Slow Suicide?

I found the second theory, the apoptosis error, a lot more disturbing until I saw the more common phrase for apoptosis: programmed cell death and learned that “between 50 and 70 billion cells die each day due to apoptosis in the average human adult.” But from what I can figure, it is one of those to everything there is a season/ A time to be born and a time to die problems. I have cells that aren’t observing this maxim. Moreover, it is altogether possible if not likely that a “vicious cycle” is set up involving the attacking and self-annihillating cells.

It’s like there’s this troop of cells and one company is relentlessly determined to destroy one of its own platoons, and that platoon is so traumatized that it turns its weapons on itself.

How dysfunctional is that?

The Loss of Self-Tolerance

Doesn’t this sound like a favorite topic of psychoanalysts, as in  “When did you lose tolerance for yourself?”

Sorry, it’s not. It’s a term from immunology. When your immune system is working right, you have self-tolerance. When it goes to hell in a hand basket, it’s a loss of self-tolerance.

Who Gets PBC?

Remember that this is an uncommon disease: PBC has a worldwide prevalence of approximately 5/100,000 ( 5 out of a 100,000 people have it), and an annual incidence of approximately 6 out of  a 1,000,000 (6 out of a million people will be newly diagnosed in a year).

  • Children don’t get it. In fact, it is unusual in teens and young adults up to about age 25.
  • About 90% of those who have it are women.
  • The highest number of cases have been found in the UK, Scandinavia, Canada, and the US. The lowest is in Australia. This may have more to do with health care procedures than with the illness.
  • Some of the hypotheses about factors associated with increased risk include:
  • living near contaminated land
  • hormone replacement therapy
  • frequent use of nail polish
  • smoking
  • appendectomy or other abdominal surgeries
  • tonsillectomy
  • More on these topics:

    More from

    Autoimmunity is a large disease category that contains almost 100 diseases. They are called “autoimmune diseases“. They are caused by the body’s own immune system getting confused and wrongly attacking the body’s good cells. Which autoimmune diseases occur from the immune confusion depends on which body cells are mistakenly attacked. Some of the best known diseases that are believed to be autoimmune include juvenile diabetes, lupus, celiac disease, multiple sclerosis, and many less common ones.

    Autoimmunity as a theory states that the immune system itself gets tricked into killing good normal cells. The immune system wrongly makes antibodies to normal cells, which cause these cells to be attacked and killed, just as if they were recognized as unhealthy virus-infected cells. The key questions about the cause of autoimmune diseases are:

    • Triggers: what starts the immune system on the wrong path?
    • Conversion: what causes the immune system to respond to the trigger?
    • Progression: what makes the immune system keep on with the autoimmune response?

    The article concludes that:

    . . autoimmunity itself is only a theory, and in fact a relatively recent theory from the last few decades.  . . . There could be other possible theories of autoimmune diseases. If we assume that the disease involves cell death (another assumption), then a list might look something like:

    • Theory 1: Autoimmunity: immune system kills the cells
    • Theory 2: Apoptosis error: cells commit suicide for some aberrant reason, and the immune system is only there to clean up afterwards
    • Theory 3: External cell damage: some virus, bacteria, toxin, or event kills the cells, and the immune system cleans up

    The following is from a sort of state-of-the-art review article (it refers to 332 articles) on PBC available on PubMed [ID#: PMC2758170] and originally published in Seminars in Immunopathology, Issue Volume 31, Number 3 / September, 2009. Authors are Simon Hohenester, Ronald P. J. Oude-Elferink and Ulrich Beuers. It is not written for the layman.

    PBC occurs in individuals of all ethnic origins and accounts for up to 2.0% of deaths from cirrhosis [15]. It primarily affects women with a peak incidence in the fifth decade of life, and it is uncommon in persons under 25 years of age. Incidence and prevalence vary strikingly in different geographic regions (as does the quality of epidemiological studies related to PBC), ranging from 0.7 to 49 and 6.7 to402 per million, respectively [16–23]. The highest incidence and prevalence rates are reported from the UK [16,21], Scandinavia [17], Canada [18], and the USA [19, 22], all in the northern hemisphere, whereas the lowest was found in Australia [20]. There is no clear evidence to support or exclude the concept of “a polar–equatorialgradient,” as it has been reported for other autoimmune conditions [24].

    A significant role for environmental factors was supported by the identification of geographic disease “hot spots,” as first reported in the northeast of England, using formal cluster analysis. The original UK analysis reported an increased frequency of PBC in former industrial and/or coal mining areas [127]. Another recent study from New York examined the prevalence of PBC and PSC near superfund areas and reported significant clusters of PBC surrounding toxic sites [128]. In synopsis, these observations gave rise to the hypothesis of a chemical environmental factor, potentially associated with contaminated land, which could either trigger disease or cause disease through a direct toxic effect [84]. This hypothesis would also provide one possible explanation for the tissue tropism of PBC if the toxin or toxins are excreted into bile (and thereby concentrated in the biliary tree) [84]. The observation that hormone replacement therapy and frequent use of nail polish are linked to the risk of developing PBC further supports the potential impact of environmental factors in the pathogenesis of PBC [117]. Smoking also seems to be a risk factor for PBC and has been demonstrated to accelerate progression [117, 129]. Associations of exposure to chemical environmental compounds and xenobiotics (including drugs, pesticides, or other organic molecules) with various human autoimmune diseases have been described as summarized in [86].

    Appendectomy, other abdominal surgeries, and tonsillectomy were significantly more frequently reported in patients with PBC in an epidemiological study in North America [155]. However, an earlier population-based case control study conducted in England did not show such associations [156]. More recently, another case–control study provided evidence that there was at least no association between PBC and the occurrence of appendectomy and pointed out the selection bias present in the previous study done in North America [157].

    It is worth mentioning that autoimmunity, defined by the presence of autoantibodies and autoreactive lymphocytes, does occur naturally. It appears that such naturally occurring autoantibodies and autoreactive lymphocytes are modulators for the suppression of early infections, clearance of apoptotic bodies, immune surveillance against cancer cells, among others, as reviewed in [160]. In this not yet completely unraveled system regulating immune response, the mechanisms responsible for the development of autoimmunity and autoimmune diseases remain enigmatic.

    However, a common causative pathway to PBC, if it exists, could not yet be identified, and it is still controversial which of the outlined factors predispose most to PBC. It may well be speculated that the search for “the cause” of PBC might lead into the dark, and the identified pathogenetic factors may contribute to a different extent in each patient. Why should the cause of PBC not be variable as is the clinical picture? The latter is highly variable: We define PBC today as the presence of cholestasis and AMAs, but only 90–95% of patients are AMA-positive and some AMA-positives hardly develop PBC. Most patients respond to UDCA treatment, but one third does not and disease progression is highly variable, to mention only the most obvious variabilities. The clinical picture that, by convention, we call PBC may well emerge from an individual composition of the described and other pathological factors.

    Once an autoimmune reaction is initiated, various vicious cycles are conceivable. Inflammatory reaction secondary to loss of tolerance will lead to further cholangiocellular damage and apoptosis, increasing presentation of (altered) self-PDC and increase autoreactivity. Once bile duct loss and cholestasis are established, retention of bile salts and other toxic compounds perpetuates damage to BECs and subsequently to the entire liver. Maintenance of these vicious cycles may be supported by an immune system that is genetically dysregulated and insufficiently capable of suppressing autoimmune reactions.


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