Everything You Need To Know About HLA Gene Variants + Their Connection to Mold, Lyme, and Chronic Fatigue

What are HLA gene variants?

​​Human Leukocyte Antigen (HLA) gene variants, are a group of genes that play a crucial role in your immune system. Think of it like this, your immune system is a vigilant guardian, always on the lookout for anything that might threaten your body's harmony. And HLA genes? Well, they're the ones that wave the flags, helping our immune cells differentiate between who’s invited to the party and who’s trying to crash it.

Like genetic snowflakes, HLA genes are incredibly unique and diverse from person to person. They're located on chromosome 6 and are categorized into three main classes: 

• Class I HLA Genes (HLA-A, HLA-B, HLA-C): These genes encode proteins that are found on the surface of almost all nucleated cells in the body. They present antigens derived from within the cell, such as viral or tumor antigens, to cytotoxic T cells. These T cells can then eliminate the infected or abnormal cells.
• Class II HLA Genes (HLA-DP, HLA-DQ, HLA-DR): These genes encode proteins that are mainly present on the surface of antigen-presenting cells like dendritic cells, macrophages, and B cells. They present antigens derived from extracellular pathogens to helper T cells, which coordinate and regulate the immune response.
• Class III HLA Genes: These genes are involved in various immune and inflammatory responses, but they don't play a direct role in antigen presentation. They encode proteins like complement components and cytokines.

Now, here's where it gets really interesting. The polymorphic nature of HLA genes means that different individuals can have different combinations of alleles (gene variants) for each HLA gene. This diversity is important for the immune system's ability to recognize a wide range of antigens, but this uniqueness can also influence how you respond to different health challenges, from infections to autoimmune issues. Sometimes, these genes can be like a double-edged sword. They offer diversity in our immune response, but certain variants might predispose us to specific health conditions. 

What health problems are caused by HLA gene variants?

Researchers are continuing to look at the relationship between different HLA gene variants and their connection to certain health problems, but these are some of the most well-researched conditions linked to HLA gene variants.

1. Lyme disease

Although Lyme disease is caused by an infection of the bacteria B. burgdorferi, research is beginning to look at the influence certain HLA gene variants have over a person’s susceptibility to Lyme disease. While more research needs to be done on the specific mechanisms behind these variants and Lyme disease, studies have studies have shown (1) that certain HLA-DRB1 variants, such as HLA-DRB10401, might be associated with an increased risk of developing Lyme disease or experiencing more severe symptoms if infected.

READ MORE: The Truth About Chronic Lyme Disease (And How to Treat It)

2. Autoimmune conditions

Due to their involvement in immune regulation, there are many HLA gene variants that can increase your risk of developing an autoimmune disease. Here are a few examples of autoimmune diseases and their associated HLA gene variants:

• Rheumatoid arthritis (RA): HLA-DRB1 gene variants are strongly associated with rheumatoid arthritis. HLA-DR4 and HLA-DR1 are among the variants most commonly linked (2) to RA.
• Type 1 Diabetes: HLA-DQ2 and HLA-DQ8 gene variants are associated with an increased risk (3) of type 1 diabetes.
• Celiac Disease: Interestingly enough, the same variants that are linked to Type 1 Diabetes - HLA-DQ2 and HLA-DQ8 - are also linked (4) to celiac disease and may even occur together, with 90–95% (5) of those with celiac disease carrying the HLA-DQ2 variant and 5-10% of people carrying the HLA-DQ8 variant.
• Multiple Sclerosis (MS): Different HLA gene variants, including HLA-DRB11501 and HLA-DRB50101, are associated (6) with an increased risk of developing multiple sclerosis. 
• Systemic Lupus Erythematosus (SLE): Studies have found that the HLA-DR3 and HLA-DR15 variants are linked (7) to an increased risk of systemic lupus erythematosus.

3. Mold toxicity

Two HLA gene variants - HLA-DRB1 and HLA-DQB1 - have been linked to an increased susceptibility to mold-related health issues and a heightened sensitivity to mold exposure and mycotoxins. In fact, one study (8) found that children with these gene variants experienced moderate to severe symptoms of asthma when exposed to mold compared to their peers without these variants who only experienced mild asthmatic symptoms from mold exposure.

Although you are more likely to be sensitive to mold with these variants, whether or not you have any other underlying health problem, the type of mold you are exposed to, and for how long ultimately determines your development of mold toxicity. 

4. Chronic fatigue

While more research needs to be done, some studies have found a link (9) between CFS and certain HLA gene variants. Researchers also believe CFS is highly associated with HLA gene variants because these variants are present in certain conditions like autoimmune disease and infections like lyme disease which directly contribute to symptoms of chronic fatigue.

How do I test for HLA gene variants?

HLA gene variant testing is typically done through blood work. Since at-home tests like 23andMe and AncestryDNA only offer limited information on HLA genes, working with your doctor is your best option to get a comprehensive look at your genetics. They will be able to recommend the right labs to get the most accurate look at your genetics to determine your individual susceptibility to certain diseases.

The Takeaway

Ultimately, understanding your HLA gene variants can be a game-changer for your health. Even if you have a genetic predisposition for a certain health problem, once you know, you’ll be able to identify the right steps you need to take to prevent these conditions from becoming a reality or to help you find healing. 

In my telehealth functional medicine clinic, we specialize in personalized healthcare and identifying the root cause of your health problems. Part of this approach is through comprehensive lab work like this that looks at your genetics. If you are ready to take the next step in your health journey, schedule a telehealth consultation today to learn more about how we can help you with functional medicine.

As one of the first functional medicine telehealth clinics in the world, we provide webcam health consultations for people around the globe.

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