Autoimmune conditions are the third most common chronic health condition following heart disease. There are over 80 different types of diagnosed autoimmune conditions, and dozens of other conditions are suspected as being an autoimmune condition. But what causes autoimmunity, and why does someone develop a specific autoimmune condition and not another? For example, why do some people develop Graves’ Disease but not Hashimoto’s Thyroiditis, and vice versa? And why do some people have the antibodies for both of these autoimmune thyroid conditions?
Autoimmunity happens when the body doesn’t recognize its own cells and tissues as self, and this in turn leads to an immune response against these cells and tissues. Hashimoto’s Thyroiditis is a condition characterized by autoantibodies against the cells and tissues of the thyroid gland. Over time these autoantibodies frequently cause sufficient damage to the thyroid gland, which prevents it from producing adequate amounts of thyroid hormone. On the other hand, Graves’ Disease involves autoantibodies against the TSH receptor antibodies, which in turn causes the thyroid gland to secrete an excessive amount of thyroid hormone.
On a short term basis it is usually far worse to have Graves’ Disease, as while the antibodies aren’t causing damage to the thyroid gland, the excessive production of thyroid hormone can result in extreme cardiac symptoms, and in some cases can even be life threatening. In addition, some people have thyroid eye disease, where the TSH receptor antibodies will attack the tissues of the eyes. Unlike some cases of Graves’ Disease, most cases of Hashimoto’s Thyroiditis aren’t considered to be emergency situations. With that being said, many people with Hashimoto’s Thyroiditis have severe and sometimes debilitating symptoms. And over the long term, if the autoimmune response isn’t addressed then there is a good chance the person with Hashimoto’s Thyroiditis will become hypothyroid, and thyroid hormone medication might be necessary to take.
Why Do People Develop Graves’ Disease and Hashimoto’s Thyroiditis?
As I mentioned earlier, there are many different autoimmune conditions. But why does autoimmunity develop, and what factors determine whether someone will develop an autoimmune thyroid condition, or another autoimmune condition such as rheumatoid arthritis or multiple sclerosis? Well, there are a combination of different factors which determine whether someone will develop an autoimmune condition. First of all, in most cases a genetic marker is required. I’m going to talk more specifically about this shortly. Second, there needs to be some type of an environmental trigger, such as a food allergen, toxin, or infection. Even stress can potentially be a trigger of autoimmunity.
In addition, some researchers speculate that a third factor is required to develop an autoimmune condition, which is hyperpermeability of the small intestines, also known as a leaky gut. As of now this still remains controversial, and I have written about this controversy in past blog posts, specifically in a post entitled “Is A Leaky Gut Present In All Autoimmune Conditions? [1]“. In this post I discussed how many of my patients with Graves’ Disease and Hashimoto’s Thyroiditis have a leaky gut, but I also have had some patients with elevated autoantibodies test negative for a leaky gut using either the classic lactulose/mannitol test, or the Array #2 from Cyrex Labs. Perhaps neither of these tests are 100% accurate in confirming the presence of a leaky gut, but it’s also possible that not everyone with an autoimmune condition has an increase in intestinal permeability.
The Role of Human Leukocyte Antigen (HLA) In Autoimmunity
I prefer to keep my articles and blog posts easy to understand, but the next few paragraphs might be a little bit advanced for some people. Different autoimmune conditions will have different types of genetic markers, and something called human leukocyte antigen (HLA) is a type of genetic surface marker. Keep in mind that there still is a lot to learn in the world of autoimmunity, as some of the autoimmune mechanisms discussed in journal articles are hypothetical, including what I mentioned earlier about intestinal permeability possibly being a factor in all autoimmune conditions. But it is a fact that there are different genetic surface markers, and someone who has Graves’ Disease will have different genetic surface markers than those people who have Hashimoto’s Thyroiditis. And there are some people who have the genetic surface markers for both Graves’ Disease and Hashimoto’s, which is why some people will have both types of autoantibodies.
What makes this complex is that an autoimmune condition can have more than one genetic surface marker which predisposes the person to developing multiple autoimmune conditions, and some autoimmune conditions share the same surface markers. With regards to HLA, it’s also beneficial to understand that these genetic surface markers aren’t just a factor in autoimmune conditions, but in other chronic health conditions as well, such as cancer. With regards to autoimmunity, people with certain HLA types are more likely to develop an autoimmune condition. However, just having a specific HLA genetic surface marker doesn’t mean that the person will develop autoimmunity.
For example, many people are familiar with the HLA markers associated with Celiac disease, which are HLA-DQ2 and HLA-DQ8. If someone has one or both of these markers it doesn’t necessarily mean that they will develop Celiac disease. This is true even if they consume gluten, which is the environmental trigger associated with Celiac disease. So what this tells us is that having a genetic marker and being exposed to an environmental trigger doesn’t always lead to autoimmunity.
Let’s look at another example. Someone with Graves’ Disease might have the genetic surface marker HLA-DR3. Unlike Celiac disease, there is no specific trigger that is associated with all cases of Graves’ Disease, as it appears that numerous factors can trigger the autoimmune response in this condition. And the same is true with Hashimoto’s Thyroiditis and many other autoimmune conditions. In any case, someone with the genetic surface marker HLA-DR3 who is exposed to a certain environmental trigger (i.e. chronic stress, H. Pylori), might develop Graves’ Disease, whereas another person with the same surface marker who is exposed to the same trigger might not develop Graves’ Disease. What makes it even more challenging is that other autoimmune conditions can also have the genetic surface marker HLA-DR3, such as Sjogren’s syndrome and systemic lupus erythematosus.
The Importance of Regulatory T Cells In Preventing Autoimmunity
While this might be confusing to some people reading this, what hopefully is clear at this point is there are factors other than genetics and environmental triggers which will determine whether someone will develop an autoimmune thyroid condition, or any other autoimmune condition for that matter. One of these factors is something called regulatory T cells, as these are immune cells which help to prevent autoimmunity from occurring. I’m not going to discuss this in detail, as in the past I wrote a separate blog post on this topic entitled “Regulatory T Cells and Thyroid Autoimmunity [2]“. But essentially, if someone has a healthy immune system, they will have plenty of regulatory T cells, and this will help to prevent them from developing an autoimmune condition. On the other hand, over a period of years, if someone eats a poor diet, is constantly stressed out, and/or doesn’t get quality sleep each night, then this will lead to a decrease in regulatory T cells, and will increase the likelihood of the person developing autoimmunity.
So a very likely scenario is that someone has the genetic surface marker for Graves’ Disease, Hashimoto’s Thyroiditis, or another autoimmune condition, and despite being exposed to numerous environmental triggers they don’t develop autoimmunity unless their body reaches a point where there isn’t enough regulatory T cells present to keep autoimmunity in check. However, certain factors can potentially affect the number of regulatory T cells, such as a chronic infection, a leaky gut, mitochondrial dysfunction, and nutrient deficiencies such as low vitamin D levels. Autoimmunity is very complex, and as I mentioned earlier, there is still a lot we don’t know about autoimmune conditions.
In the next blog post I’ll discuss the autoimmunity timeline, and will go over the different stages of autoimmunity. Most people reading this know that it takes time for thyroid autoimmunity to develop, and these four stages should allow you to better understand why many people with these conditions don’t receive proper care until the later stages. Plus, since there is a genetic component involved with most, if not all cases of Graves’ Disease and Hashimoto’s Thyroiditis, if you have either of these conditions then you probably will want to share this information with your siblings and children, as it can help to prevent someone from developing a full blown autoimmune condition.