The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 60

74. Is mast cell activation the cause of many other diseases?

No, but it is involved in many other diseases.

I write a lot about mast cells and the way they are involved in various other conditions. Mast cells live throughout the body in many tissues. Because they are in so many tissues, their role in many diseases is well researched.

Mast cell activation is not the same as mast cell activation syndrome. I have written about this here. Basically, there are tons of things in the body that cause mast cell activation. These are conditions where we want or need mast cells to become activated because then the mast cells help keep our body working the way it is supposed to. For example, during a woman’s menstrual cycle, if mast cells could not become activated the way they normally do, a woman’s period could become very irregular. This in turn could affect the amounts and types of hormones in a person’s body, causing symptoms and problems.

Situations where mast cells normally become activated include labor and delivery, during any type of infection, during situations where the GI tract is inflamed, when your body is growing new blood vessels, any time your body is healing, and when you have cancer or a tumor. In these situations, the mast cells activate to send signals to other cells in the body to help regulate what is happening. Mast cell activation is not always bad. It is, in fact, a normal and necessary process that happens in the body of everyone every day. Mast cell activation is necessary to stay alive.

Now let’s look at the role of mast cells in diseases that are not mast cell diseases.

When I was little, I was a Girl Scout for three weeks before I got kicked out. (This is true and not related to mast cell activation.) There was a game that we used to play called “Telephone.” During this game, everyone would sit in a big circle. One person would think up a short sentence and whisper it into the ear of the person next to her, who would in turn whisper into the ear of the person next to them, and so on. Often, people misheard the sentence and so it was completely wrong by the time it got back to the person who started it.

Diseases in the human body are like a very complex game of Telephone. In every disease, many cells that did not cause the disease can cause symptoms even though they are not the cause. The way to know if a disease is a true mast cell disease is to know which cell first messed up the sentence in the game of Telephone.

Here’s what this sounds like in people:

Lisa says to Pari: Puff the magic dragon

Pari says to Dana: Puff the magic dragon

Dana says to Celeste: Puff’s magic is dragging

Celeste says to Lisa: Puff’s magic is dragging

So in this situation, Dana changed the sentence. Because she changed it, Celeste also had the sentence wrong. So Dana caused the problem. Celeste did not. (In real life, Dana is lovely and not a problem.)

When your body has a disease, the symptoms and damage are caused by cells giving or receiving messages incorrectly. Instead of using words to talk to each other, cells use molecules. Even though they use molecules to talk to each other, it is very much like a language. If the message is “said” wrong in this cell language, then all the cells after the mistake are doing things that are unhelpful or dangerous. However, they are NOT the cause of the disease because they are not the one that changed the message.

Now let’s look at this with cells in the human body during a disease. I’m going to use a very simplified explanation of rheumatoid arthritis as an example.

T cell says to B cell: I think our body is dangerous to us!

B cell says to T cell: Oh, snap! Let’s get the word out!

B cell needs to tell the body about this danger. It makes a message that says, “Danger right here! Danger!”

B cell says to mast cell: WE ARE IN GRAVE DANGER! ATTACK! ATTACK!

Mast cell to other cells: KILL THIS INVADER KILL IT TO DEATH

Except there is no invader. It is just your regular joints being regular and not dangerous.

Other cells: *trying to kill your joints*

Joints: Uh, guys, I’m actually supposed to be here –

Mast cell: I CAN’T HEAR YOU OVER THIS SCREAMING B CELL

Let’s recap.

T cell gives the B cell bad information. This causes B cell to alert other cells of “danger.” But this wasn’t the B cell’s fault. It was the fault of the T cell which gave the B cell bad information. And that means that everything that comes after the T cell giving the B cell the bad information makes the problem worse but is not really the cause of the problem.

I used rheumatoid arthritis as an example because a lot of treatment of rheumatoid arthritis revolves around blocking those danger signals from mast cells. But is the mast cell the cause of the rheumatoid arthritis? No, it is not. It is not the cause because mast cells have to respond to commands from B cells in order to help protect us against infection and do other helpful things. The mast cell did not decide the joints were dangerous. The B cell told the mast cell this so the mast cell is working with bad information that it doesn’t realize is bad.

If the mast cell isn’t the cause of the rheumatoid arthritis, why do we bother blocking mast cell signals instead of telling the T cell and B cell to be quiet? Because quieting the mast cell signal will help with symptoms and we know how to quiet the mast cell signal and we don’t always know how to quiet the other signals. Stopping the mast cell signal can make symptoms much better but it does NOT cure rheumatoid arthritis. Why? Because mast cells do not cause rheumatoid arthritis.

So mast cells are involved in many diseases without causing most of them. The way you can tell they are not the cause is that they did not start the wrong “message” that caused the symptoms and damage.

Now, I would like to address the fact that there are some diseases that have some research to suggest that they may genuinely be a form of mast cell activation disease. Fibromyalgia is one of these diseases. However, at this time, there is not enough evidence for it to be classified as a mast cell disease.

I tried to be as clear as possible about a very complicated topic. If I didn’t do it well, tell me and I’ll have another go at it.

(Author’s note: This is a SUPER simplified version of rheumatoid arthritis. RA is an autoimmune disease and it is still not clear exactly how the T cells and B cells start sending the wrong messages in an autoimmune disease. I just simplified it here to make it easier to see my point.)