Primary biliary cirrhosis

Primary biliary cholangitis and cirrhosis, or PBC, is an autoimmune disease where the T cells attack the cells that line the smaller-sized bile ducts in the liver.

As the cells are damaged or destroyed by immune attack, they start letting bile leak through their tight junctions and into the interstitial space, where it can get into the blood and the other liver cells.

This can cause inflammation and symptoms that are similar to cholestasis and obstructive jaundice, both of which there’s some disturbance in bile flow.

At first it presents as chronic inflammation, which is where it gets the name cholang-itis, for inflammation of the bile ducts, but advanced stages of the disease leads to cirrhosis as more cells are destroyed both from the autoimmune attack and infiltration of bile.

As with a lot of autoimmune diseases, the exact reason why T-cells start attacking these bile duct cells is unknown, and it’s likely related to genetic predisposition in combination with environmental triggers, and is associated with other autoimmune diseases like autoimmune hepatitis and Sjogren’s syndrome.

PBC tends to affect women at a much higher rate than men, about a 9:1 female to male ratio.

For some reason that has yet to be completely figured out, in almost all cases of PBC, your body creates antibodies to mitochondria, specifically a mitochondrial protein called PDC-E2; for that reason, one of the most notable markers in PBC are these antibodies to mitochondrial proteins (or AMAs) in the patient’s blood, as many as 95% of patients with PBC have AMAs in their blood.

Why though, are the bile duct cells specifically targeted? Don’t all cells have mitochondria? Shouldn’t these AMA’s be targeting all cells then?

One theory is based on a concept called molecular mimicry, where the antigens that bring about this autoimmune response are really similar to another protein, but different enough so that the immune system gets confused and thinks it’s a foreign version of that particular protein.

Here’s an example of two people’s cells, they both have this triangle protein, but they have different colored triangles, each person’s immune knows that these are their own proteins, their own self-proteins and that they shouldn’t attack, but they have antibodies for proteins that are very similar, but definitely different from self, so say they have antibodies for triangles, just different colored triangles, so like person A has red, yellow, and blue, just not green, and person B has green, yellow, and blue, and not red. So both these people’s immune systems are like yep, these are all self so we’re good.