Published December 12 2016
If you have Graves’ Disease or Hashimoto’s Thyroiditis, did you ever wonder why you developed this condition in the first place? Sure, genetics is a factor, and if you have been reading my articles and blog posts for awhile then you probably realize that an environmental trigger is also necessary. And if you’re familiar with the triad of autoimmunity then you’re aware that in addition to a genetic predisposition and environmental trigger, an increase in intestinal permeability (a leaky gut) probably is a requirement as well. But the truth is that someone with a genetic predisposition who has a leaky gut and is exposed to an environmental trigger won’t develop autoimmunity unless if they also have something else…a loss of self tolerance.
What does this mean when I say that those people with Graves’ Disease and Hashimoto’s Thyroiditis have a loss of self tolerance? Well, under normal circumstances the immune system recognizes our tissues and organs as being “self”. This of course is very important, as if the immune system doesn’t recognize our tissues and organs as being “self”, then it will treat our tissues and organs like a foreign invader and mount an attack. Well, this is essentially what happens in autoimmune conditions. So for example, with Graves’ Disease the immune system attacks the TSH receptors, which is why someone with this condition will have elevated TSH receptor antibodies. And with Hashimoto’s Thyroiditis the immune system will attack the thyroid peroxidase enzyme, the thyroglobulin proteins of the thyroid gland, or both of these.
So am I suggesting that someone who has a genetic predisposition for Graves’ Disease or Hashimoto’s, has a leaky gut, and is exposed to an environmental trigger won’t necessarily develop this condition unless if they also have a loss of self tolerance? This is exactly what I’m suggesting. For example, stress is a potential trigger of autoimmune thyroid conditions, but most people with a genetic predisposition for Graves’ Disease or Hashimoto’s Thyroiditis don’t develop that condition when dealing with stress, even if they also have a leaky gut. So when we talk about the “triad of autoimmunity”, while the three factors mentioned might be required for autoimmunity to develop, this doesn’t mean that they are the only factors.
How Do People Develop A Loss of Self Tolerance?
There are numerous ways in which someone can develop a loss of self tolerance, and so let’s go ahead and discuss some of the common ways:
1. Exposure to an environmental trigger. This may seem confusing based on what I said earlier, as I mentioned how someone who has a genetic predisposition for thyroid autoimmunity who has a leaky gut and is exposed to an environmental trigger won’t develop an autoimmune thyroid condition unless if they also have a loss of self tolerance. But here I’m saying that exposure to an environmental trigger can result in a loss of self tolerance. While it is true that certain environmental triggers can lead to a loss of self tolerance, this isn’t always the case, and as I’ll discuss below, other factors can lead to a loss of self tolerance.
2. Certain genetic polymorphisms. There is evidence that a genetic polymorphism (a common genetic defect) of thyroglobulin or the TSH receptor can make someone more susceptible to developing a loss of self tolerance (1)  (2) . Of course this is one factor that can’t be changed, although all of the other factors I’m listing can be modified.
3. Decrease in regulatory T cells. I’ve spoken about the importance of regulatory T cells in other articles and blog posts. Regulatory T cells help to suppress autoimmunity, and so it’s not surprising that a decrease in regulatory T cells can result in a loss of self tolerance.
4. Low selenium levels. Numerous studies have shown that selenium can lower thyroid antibodies. And one of the main reasons for this might be due to its effects on regulatory T cells, which of course I just mentioned as playing a role in self tolerance. However, while selenium definitely benefits the immune system, it still remains unclear whether supplementing with selenium can increase the suppressive function of regulatory T cells (3) .
5. Low vitamin A levels. Having sufficient vitamin A levels is important for self tolerance, and this seems to relate to vitamin A increasing regulatory T cells (4)  (5) . And some sources question whether even a marginal vitamin A deficiency can have a profound effect on the health of the immune system (6) .
6. Intestinal dysbiosis. Many people reading this know that having a healthy gut is important in order to have a healthy immune system. But you might not know that some of the good bacteria of the gut can lead to the production of intestinal regulatory T cells (7) . Hopefully you are seeing a pattern here, as one of the main things we need to do is increase regulatory T cells, which can be increased by certain nutrients, and having a healthy gut is also essential.
Self Tolerance vs. Oral Tolerance
What is the difference between self tolerance and oral tolerance? Well, you now know that self tolerance means that the immune system recognizes your own tissues and organs as being “self”, or part of your own body. So for example, in a healthy person the immune system shouldn’t attack the cells of the thyroid gland, as it recognizes this gland as being “self”. On the other hand, oral tolerance refers to the immune system not becoming activated when you ingest an oral antigen. An example of this is when you eat a bowl of steamed broccoli. Even though the broccoli is not part of your body, your body usually knows not to mount an immune system attack. This of course is very important, as it would pose a big problem if your body reacted every time you ate something.
But why doesn’t the immune system react in a negative way every time you eat something? And how does this relate to food sensitivities? This truly is an amazing process, and there still is a lot we don’t know. The gut-associated lymphoid tissue (GALT) plays a huge role in this, as this is involved in the ingestion of dietary antigens in a way that doesn’t result in an immune reaction (8) . And at this point you probably won’t be surprised to know that regulatory T cells also play a role.
How Can We Restore Self Tolerance?
Common sense suggests that in order to restore self tolerance it is necessary to address those factors which can result in a loss of self tolerance in the first place. As I mentioned earlier, the only factor I listed that can’t be modified is if someone has a genetic polymorphism of thyroglobulin or the TSH receptors.
So the following represent the factors we want to focus on when trying to restore self tolerance:
Find and remove the environmental trigger. You of course want to detect and then remove the environmental trigger. This can be a challenge to do, as there are numerous factors which can trigger thyroid autoimmunity, and I have discussed many of these in past articles and webinars. Some examples of triggers include food allergens, infections, environmental toxins, and even stress can be a trigger by dysregulating the immune system. Finding the trigger is usually accomplished through a thorough case history and the appropriate testing.
Heal the leaky gut and correct intestinal dysbiosis. Just as a reminder, in order to have a healthy immune system you need to have a healthy gut. As a result, if you have an increase in intestinal permeability (a leaky gut) then this needs to be corrected. The same applies to intestinal dysbiosis, which is an imbalance of the gut flora. And while intestinal dysbiosis can mean that there is the presence of a pathogen (i.e. parasite), this isn’t always the case. Many times dysbiosis is caused by low amounts of good bacteria, although over time this can lead to an overgrowth of pathogenic yeast (i.e. Candida Albicans) or bacteria.
Of course eating well is also important. An autoimmune paleo diet is commonly recommended for those with Graves’ Disease and Hashimoto’s Thyroiditis, and this diet excludes foods that are allergenic and can increase the permeability of the gut. However, one of the downsides of this diet is that many people don’t eat enough vegetables, which serve as a source of fiber and prebiotics, which in turn can feed the good bacteria and improve the health of the gut. Fermented vegetables can be a good source of probiotics. While there might be certain situations when these foods aren’t tolerated (i.e. small intestinal bacterial overgrowth), in most cases people following an autoimmune paleo diet should be eating plenty of these foods.
Increase regulatory T cells. I mentioned earlier how a decrease in regulatory T cells can result in a loss of self tolerance, and so you want to do things to help increase Tregs. In this article I specifically spoke about improving the health of the gut, as well as having healthy levels of selenium and vitamin A. But there are other factors which can increase regulatory T cells, and I wrote a separate blog post on this entitled “Regulatory T Cells and Thyroid Autoimmunity “.
So hopefully you have a better understanding of what a loss of self tolerance entails, and realize that there isn’t a single mechanism responsible for a loss of self tolerance. Some of the reasons why someone develops a loss of self tolerance includes exposure to an environmental trigger, genetic polymorphisms, and a decrease in regulatory T cells, which can be caused by nutrient deficiencies and/or intestinal dysbiosis. And so when trying to restore self tolerance we of course want to address these factors.