What is HLA typing for coeliac disease?

Liz Wood Alphabiolabs

By Liz Wood, Health Testing Specialist at at AlphaBiolabs
Last reviewed: 07/05/2024

In this article, we discuss HLA typing for coeliac disease including what it is, how it relates to coeliac disease, and how you can get HLA typing to assess your risk of developing coeliac disease.

What is coeliac disease?

Coeliac disease is a hereditary, autoimmune disease that develops over time due to an adverse reaction to gluten.

Gluten is a protein found in cereal grains including wheat, barley and rye, and is commonly used in food products such as cereal, bread and pasta.

When a person with coeliac disease eats gluten, the body reacts by launching an immune response. This immune response causes the body to attack its own tissues, causing damage to the lining of the gut. If the gut lining becomes damaged, this makes it more difficult for the intestines to absorb the necessary nutrients from food.

Coeliac disease can also cause painful or unpleasant symptoms such as bloating, flatulence, abdominal pain or cramps, diarrhoea, nausea, and vomiting.

However, some people may not have any symptoms at all, or their symptoms may be very mild. This is known as ‘silent’ coeliac disease.

If left untreated, coeliac disease can lead to more severe symptoms or complications, such as fatigue, problems with fertility, anaemia, nerve damage or osteoporosis.

Unfortunately, there is no cure for coeliac disease. The only treatment is to adhere to a strict, life-long gluten-free diet.

When people with coeliac disease stop eating gluten, their intestines begin to heal, and the symptoms can disappear altogether.

Everything you need to know about coeliac disease

What does HLA mean?

HLA stands for Human Leukocyte Antigens.

HLA are a group of genes found on chromosome 6 that provide instructions on how to make special proteins. These special proteins make up the HLA complex.

The HLA complex is divided into two major classes:

  • Class I molecules – which can be found on lots of different cells in the body, and
  • Class II molecules – which are only found on specific cells of the immune system.

The role of these HLA proteins is to help the immune system destroy foreign invaders within our bodies, such as harmful viruses or bacteria.

The HLA proteins present parts of the invader to other immune cells, triggering an immune response.

However, sometimes HLA proteins do not work as expected. When someone has certain types of HLA genes, they have different instructions, and therefore make slightly different HLA proteins.

In the case of coeliac disease, people with HLA-DQ2 or HLA-DQ8 make class II HLA proteins that bind very easily to gluten components.

They then present these components to special immune cells, which triggers an immune response in the body. This immune response damages the lining of the gut, which in turn causes unpleasant symptoms.

What is HLA typing?

HLA typing is a scientific method used to identify which HLA alleles (genetic variations) a person has.

Experts have identified over 9,000 different HLA alleles. This means that the combination of HLA alleles each person has is extremely diverse.

This variation from person-to-person is important because it means our immune systems are better equipped to fight disease.

But why would you need to find out which HLA variants a person has?

  • Tissue or organ transplants

    For tissue or organ transplants, the HLA variants of the donor and receiver are tested.

    The closer the HLA match between donor and recipient, the more likely it is that the tissue/organ transplant will be successful.

    If they do not match, the body thinks that the donated tissues are a foreign invader and will launch an immune response, which can have devastating consequences for the person who has received the donated tissue/organ.

  • Diseases

    HLA typing can be used to determine whether a person is at risk of developing certain diseases.

  • Drug sensitivity

    It can also be used to determine a person’s sensitivity to certain drugs.

Having certain HLA gene variants can make you more likely to suffer with certain autoimmune conditions.

For example, HLA-B27 is associated with various types of arthritis, and the HLA-DQ2 and/or HLA-DQ8 genes are associated with an increased risk of developing coeliac disease and type 1 diabetes.

HLA typing can therefore help you find out whether you are at risk for certain autoimmune conditions. It can also help you fast-track a diagnosis via your doctor if you think you might be suffering from an autoimmune condition.

How is HLA typing performed?

In the past, HLA typing was performed using a serological method.

The patient’s blood would be mixed with a serum that contained antibodies to HLA. If there was a match between the blood of the patient and the HLA antibodies, a colour change would occur.

This method, although quick and cheap to perform, was not always successful, due to the large variety of HLA alleles that exist.

Many laboratories have adopted new and more effective approaches, such as electrophoresis or next generation sequencing.

At AlphaBiolabs, we perform HLA typing for coeliac disease using real-time polymerase chain reaction (RT-PCR).

RT-PCR is a quick, reliable, and effective method for identifying HLA alleles that are associated with an increased risk of developing coeliac disease.

What are the HLA genes associated with coeliac disease?

The HLA genes linked to coeliac disease are HLA-DQ2 and HLA-DQ8.

These genes are made up of genetic variants (alleles). If you have these genes, you are more likely to develop coeliac disease than the rest of the general population.  

HLA-DQ2

There are two types of HLA-DQ2 genes: HLA-DQ2.5 and HLA-DQ2.2.

HLA-DQ2.5 carries the highest risk for coeliac disease. Around 90-95% of people with coeliac disease have this haplotype.

Additionally, people who have two copies of HLA-DQ2.5 have at least a 5 times higher risk of developing coeliac disease than those with just one copy of HLA-DQ2.5.

HLA-DQ2.2 is said to be a low-risk gene for coeliac disease. This is because only a very small percentage of people with coeliac disease have this haplotype (a set of DNA variations/polymorphisms that tend to be inherited together).

HLA-DQ8

People with the HLA-DQ8 gene are said to be at moderate risk of having or developing coeliac disease. Approximately 5% of people with coeliac disease have the HLA-DQ8 gene.

What are the benefits of HLA typing for coeliac disease?

HLA typing can be beneficial if you suspect that you may have coeliac disease and want to find out if you carry the genes associated with coeliac disease.

A genetic test/HLA typing for coeliac disease can:

  • Help you find out whether you are at risk of developing coeliac disease in the future. This is especially useful if you have a first-degree relative with coeliac disease, as research shows that people with coeliac disease have a higher risk of passing the disease down to first-degree relatives (i.e. parents to children).
  • Help you to obtain a faster diagnosis from your doctor.

    It is important to note that HLA typing cannot be used to diagnose someone with coeliac disease. This is because roughly 30-40% of the general population have the HLA-DQ2 and/or HLA-DQ8 genes, but do not have coeliac disease.

    However, it is a very useful tool, as the HLA-DQ2 and/or HLA-DQ8 genes are found in all people with coeliac disease.

    Therefore, if you have either/both genes, you can share the test results with your doctor to support a case for further, diagnostic tests (such as a blood test and/or gut biopsy).

  • Help you rule out coeliac disease as the cause of your symptoms.

    If you do not carry the HLA-DQ2 or HLA-DQ8 genes, it is extremely unlikely that you will ever develop coeliac disease.

    An AlphaBiolabs Genetic Coeliac Disease Test can tell you whether you have the HLA-DQ2 and/or HLA-DQ8 genes, and whether you are at high, moderate, low or no risk of developing coeliac disease in the future.

The role of gluten and HLA-DQ2/HLA-DQ8 in people with coeliac disease is quite complex.

Gluten is a protein. When you eat gluten, the body breaks it down into two smaller components called gliadin and glutenin.

Normally, these components pass through the intestines and are excreted in your faeces.

However, in people with coeliac disease, gliadin can pass through the walls of your intestines. The gliadin binds to an enzyme called tissue transglutaminase. This enzyme makes changes, or ‘modifies’, the gliadin.

Special immune cells, such as dendritic cells, have HLA class II proteins on their cell surface.

This is where the HLA-DQ2/HLA-DQ8 genes come in – people with these genes make HLA-DQ2 and/or HLA-DQ8 proteins that are found on the surface of these cells of the immune system.

The HLA-DQ2 and HLA-DQ8 proteins preferentially bind to these modified gliadin molecules – in other words, they stick together well.

When this happens, an immune response occurs, causing lots of inflammation.

Another type of immune system cell, B cells, are then activated. They make antibodies against the tissue transglutaminase enzyme.

This is why doctors test your anti-tTG levels if they suspect you of having coeliac disease.

You’ll often see the statement: HLA-DQ2/HLA-DQ8 genes are necessary, but not sufficient, to develop coeliac disease.

This means that to have coeliac disease, you have to have the HLA-DQ2/HLA-DQ8 genes, but there are other factors involved that are needed for coeliac to develop.

These factors may not be the same for everybody. There could be another genetic cause that triggers the onset of coeliac disease.

There are also environmental factors, such as illness or injury to the gut, which can cause coeliac disease to develop.

The HLA-DQ2.5 haplotype infers the highest risk for developing coeliac disease. Approximately 90-95% of people with coeliac disease have this haplotype.

Almost everyone else has HLA-DQ8, and a very small percentage will have HLA-DQ2.2.

However, it is estimated that roughly 30-40% of the general population also have these genetic variants, and so identifying the HLA-DQ2 or HLA-DQ8 genes is not enough to diagnose someone with coeliac disease.

HLA typing for coeliac disease is, however, a very good indicator of whether you are unlikely to ever develop coeliac disease.

This is because the HLA-DQ2 or HLA-DQ8 genes are necessary for coeliac disease to occur, so if you do not have either of these genes, it is extremely unlikely you will ever develop coeliac disease.  

Where can I get an HLA-DQ2/HLA-DQ8 test?

A genetic HLA-DQ2/HLA-DQ8 test can be useful to determine whether you are at risk of having or developing coeliac disease, before you undergo any invasive diagnostic testing.

Diagnostic testing for coeliac disease usually includes blood testing for antibodies and, depending on the results of the blood test, a gut biopsy to assess any damage to the gut lining.

The AlphaBiolabs Genetic Coeliac Disease Test can tell you whether you have the HLA-DQ2 or HLA-DQ8 genes linked to coeliac disease.

Our simple, at-home test is quick and completely pain free, with only two buccal (cheek) swabs required. Results are provided in just 4-5 working days.*

The results of the test can also be shared with your doctor, to facilitate a faster diagnosis.

A negative result for the HLA-DQ2/HLA-DQ8 genes means that you are unlikely to ever develop coeliac disease. This is because these genes are necessary for coeliac disease to develop. 

It’s also important to note that simply having these genes does not necessarily mean that you will develop coeliac disease or that you are currently suffering from it.

You can order your Genetic Coeliac Disease Test online now.

Alternatively, call our friendly, knowledgeable Customer Services team on 0333 600 1300 or email info@alphabiolabs.com for more information.

How do I interpret my HLA-DQ2/HLA-DQ8 test results?

To make things easy to understand, our results tell you which alleles we identified from your sample, your HLA haplotype, and your risk for developing coeliac disease.

The test can be used to rule out coeliac disease if you do not have the HLA-DQ2 and/or HLA-DQ8 genes. This is because almost every person with coeliac disease has one or both genes.

The test cannot be used to diagnose someone with coeliac disease, however. This is because roughly 30-40% of the general population has the HLA-DQ2/HLA-DQ8 genes but will never go on to develop coeliac disease.

But the results can help you obtain a diagnosis from your doctor, particularly if you are experiencing symptoms such as bloating, flatulence, nausea, diarrhoea or vomiting.

What does a positive HLA-DQ2/HLA-DQ8 result mean?

A positive HLA-DQ2/HLA-DQ8 result means that you have the genes that are associated with coeliac disease.

Compared to the rest of the general population, you have an increased risk of having or developing coeliac disease.

If you are experiencing symptoms, you can share your result with your doctor. They will be able to help you obtain a diagnosis.

They may refer you for further testing to confirm or rule out a diagnosis of coeliac disease.

What does a negative HLA-DQ2/HLA-DQ8 result mean?

A negative HLA-DQ2/HLA-DQ8 result means you do not have the genes that are associated with coeliac disease.

If you do not have these genes, you have almost no lifetime risk of ever developing coeliac disease.

If you are having symptoms, and/or suspect you might have coeliac disease but have received a negative result, you should consult your doctor who will be able to advise on next steps for testing and diagnosis.

Genetic Coeliac Testing

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Liz Wood, AlphaBiolabs

Liz Wood

Health Testing Specialist at at AlphaBiolabs

Liz joined AlphaBiolabs in 2021, where she holds the role of Health Testing Specialist.

As well as overseeing a range of health tests, she is also the lead on several validation projects for the company’s latest health test offerings.

During her time at AlphaBiolabs, Liz has played an active role in the validation of the company’s Genetic Lactose Intolerance Test and Genetic Coeliac Disease Test.

An advocate for preventative healthcare, Liz’s main scientific interests centre around human disease and reproductive health. Her qualifications include a BSc in Biology and an MSc in Biology of Health and Disease.