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CTLA4 Gene: Autoimmune Risk Factor

Autoimmune diseases are caused by your immune system targeting and attacking cells in your body. This can result in a number of different problems: joint pain (rheumatoid arthritis), scaly, thick skin (psoriasis), hypothyroidism (Hashimoto’s), and more. It is often difficult to get a solid diagnosis with autoimmune conditions since the symptoms overlap with other conditions.

This article covers one genetic cause of increased susceptibility to several different autoimmune diseases. It dives into the variants you can check in your genetic raw data, and it gives possible solutions to investigate, based on your variants.

Keep in mind that genetic variants just add to the susceptibility to autoimmune diseases — there is usually an additional factor that triggers the disease.

CTLA-4 and Autoimmune Diseases:

The CTLA4 gene codes for a protein that is important in the immune system. It acts as a checkpoint that can downregulate your immune system response. CTLA4 is active in regulatory T cells (Tregs), which are the part of the immune system that maintains your tolerance to self-antigens.[ref][ref]

Basically, you want a powerful response from your immune system when you are exposed to a pathogen that causes a disease – pneumonia, West Nile virus, cholera, measles, flu… But you don’t want an out-of-control immune system.

Your body needs to control your immune response when it isn’t needed. Checks and balances. The Treg cells are the checks keeping your immune system from going out of control and attacking your own cells.

As an example, one way in which the body needs to deactivate the immune response is during pregnancy. Think about it — a mother’s body has an organism with foreign DNA growing in it. There has to be a system in place to keep the mother’s body from attacking the fetus. Immune checkpoint molecules (CTLA4 is one of them), keep the maternal immune system from attacking the fetus.[ref]

Consequently, when researchers decrease the amount of CTLA-4 in mice, it causes autoimmunity.[ref]

Autoimmune conditions associated with CLTA-4 include:

  • Graves’ disease (TSH-receptor autoantibodies cause hyperthyroidism)
  • Hashimoto’s disease (hypothyroidism)
  • Rheumatoid arthritis[ref]
  • Type 1 diabetes[ref]
  • Lupus[ref]
  • Vitiligo
  • Multiple Sclerosis[ref]
  • Celiac disease[ref]
  • Myasthenia gravis
  • Sjogren’s Syndrome[ref]

Keep in mind, though, that autoimmune conditions aren’t solely caused by decreased CTLA-4 levels. This is just one player in the autoimmune profile.

Checkpoint inhibitors in cancer:

The flip side of this CTLA-4 story is that inhibiting CTLA-4 is now a powerful tool in cancer therapy for certain types of cancers. Taking away the brakes on the immune system – decreasing that checkpoint for downregulating the immune system – allows the body to have a better shot at destroying cancer cells.


CTLA4 Genotype Report

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Lifehacks:

If you have an autoimmune condition, your doctor can best guide you in the new immune suppression medications on the market today.

Diet:

The autoimmune paleo (AIP) diet has been effective for many people with autoimmune diseases.

  • A clinical trial of the Autoimmune-Paleo diet showed good results for women with Hashimoto’s thyroiditis.[ref]
  • Dr. Terry Wahl’s also has a dietary protocol shown to be effective in multiple sclerosis patients.[ref]

Both of those diets focus on fresh vegetables, fresh fruits, and high-quality meats. Both diets avoid common food intolerance triggers such as gluten, dairy, and eggs.

6 Natural Supplements that may impact CTLA-4 and Autoimmune Diseases:

Vitamin D:

Multiple studies show active vitamin D (1,25 (OH)2D3) increases the expression of CTLA-4.[ref][ref] This may be part of the connection between low vitamin D and an increased risk for many autoimmune conditions.

What can you do to raise your vitamin D levels? First, you should check to see if your levels are low. Your doctor may be willing to run this for you or you can order your own test- UltaLab Tests – 1,25(OH)D test (insurance won’t pay if you order your own). Sun exposure on as much skin as possible, but not so long as to get sunburned or skin damage.[ref] If you go the vitamin D supplement route, a lot of the cheap vitamin D supplements contain soybean oil. Personally, I like the idea of coconut oil-based vitamin D supplements instead.

DHA and CTLA4 levels:

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HLA B27: Genetic Variant That Increases Susceptibility to Autoimmune Diseases
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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.