The HLA gene
HLA or the Human Leukocyte Antigen complex is a group of proteins that are involved in the regulation of the immune system of our body.
The HLA is the human equivalent of the Major Histocompatibility Complex or MHC that is found in many other animals.
The HLA gene is involved in providing the instructions for the formation of these HLA proteins.
The MHC in humans is made up of over 200 genes that are placed closely on chromosome 6 and are broadly divided into three groups:
- MHC I
- MHC II
- MHC III
There are 3 classes of the MHC I gene namely, HLA- A, HLA- B, and HLA- C.
The 6 classes of the MHC II gene include HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRA, and HLA-DRB1.
The MHC III genes are also involved in immunity and inflammation.
The histocompatibility genes have many genetic variations involving a lot of single-nucleotide polymorphisms.
Some of these variants are known to be associated with many forms of allergies.
HLA gene and gluten sensitivity
Gluten is a protein that is found in grains such as wheat, barley, and rye.
It is the component that allows the flour to rise, holds the dough and allows absorption of liquids.
This property is also used to thicken sauces and gravies.
However, there is a small percentage of people who cannot tolerate gluten and are called gluten-intolerant or gluten-sensitive individuals.
Gluten sensitivity is genetically linked.
Two genes namely HLA DQ2 and HLA DQ8 have primarily been linked to celiac disease (the most severe form of gluten sensitivity).
Other genes such as HLA DQ1 and HLA DQ3 are also believed to predispose an individual to gluten sensitivity.
Though only 1 % of the population has celiac disease, a larger part of the population suffers from gluten sensitivity.
Every individual gets two copies of the HLA DQ gene, one from their mother and one from their father.
The 2 copies of the HLA DQ gene you get determines your sensitivity to gluten.
| rsid | gene name | risk allele | implications |
|---|---|---|---|
| rs4639334 | HLA DQ 7 | A | Increased risk for gluten sensitivity |
| rs7454108 | HLA DQ 8 | C | Increased risk of developing the celiac disease and Type-1 Diabetes |
| rs2395182 | HLA DQ2.2 (M1) | T | Increased risk for gluten sensitivity. Having the T allele of the HLA DQ2.2 gene on chromosome 6 increases the risk of gluten sensitivity and celiac disease by 71% as compared to having the G allele. |
| rs7775228 | HLA DQ2.2 (M2) | C | Increased risk for gluten sensitivity. The presence of the minor C allele increases the risk of autoimmune disorders such as celiac disease and hay fever. |
| rs4713586 | HLA DQ2.2 (M3) | G | Decreased risk for gluten sensitivity |
| rs2187668 | HLA-DQ 2.5 | A | Increased risk for gluten sensitivity For most individuals, having the G/G alleles for SNP rs2187668 of HLA-DQ 2.5 gene reduces the risk of celiac disease. However, for those having the A allele, the risk increases by 2.1 times for those with A/G alleles and by 3 times for those with A/A alleles. The A allele puts the individual at risk of not just celiac disease and gluten sensitivity but also other autoimmune diseases like Lupus. |
You might also be interested in: 5 Facts You Must Know Before Deciding To Go Gluten-Free
HLA and allergy
Commonly found allergic conditions such as asthma, hay fever, and eczema occur due to increased levels of Immunoglobulin E(IgE) produced in the blood in response to certain allergens.
Out of the many studies that are currently underway to understand the nature and cause of this IgE allergic response, one genetic epidemiological study in atopic individuals shows strong associations between HLA class II genotypes and IgE response to antigens.
These HLA molecules are membrane-bound glycoproteins that bind processed antigen polypeptides and present them to T cells.
The HLA class I antigens are found on all nucleated cells and platelets and are cytotoxic in nature.
The HLA class II molecules are found mainly on B cells, activated T cells, and monocytes/macrophages.
There are many studies that have shown some form of a strong association between HLA genes and IgE mediated allergic responses.
There is still some uncertainty over the exact role of HLA class II genetic polymorphisms in triggering these responses.
But, there is a certainty that HLA genes have a crucial role to play in allergic reactions.
Hand-picked content for you: A Guide To Analyze Your DNA Raw Data For Allergy
HLA and dust mites
Dust mite allergy is a type of allergy to tiny bugs that live in house dust.
The symptoms of dust mite allergy are very similar to that of hay fever and include sneezing and runny nose.
Certain genetic variants of the HLA-DRA gene have been associated with the increased risk for dust mite allergy.
| rsid | gene | risk allele | implications |
|---|---|---|---|
| rs3177928 | HLA-DRA | A | Increased risk for dust mite allergy. The A allele of SNP rs3177928 is strongly associated with allergic reactions, including those to dust mites. The same SNP is also linked with LDL increased risk of high cholesterol and total cholesterol levels. |
HLA and pet allergy
Pet allergy is a type of allergy that occurs in individuals due to exposure to certain proteins in the saliva, hair or skin of pet animals like cats, dogs, hamsters, etc.
The symptoms of pet allergies are similar to any other allergies and include incessant sneezing, runny nose, itchy and watery eyes, nasal congestion, cough, etc.
| rsid | gene | risk allele | implications |
|---|---|---|---|
| rs7775228 | HLA-DQB1 | C | Increased risk for pet allergy. The C allele of the SNP rs7775228 of HLA-DQB1 shows increased risk of allergy to allergens in dog dander. |
| rs3177928 | HLA-DRA | A | Increased risk for pet allergy. The A allele of SNP rs3177928 is strongly associated with allergic reactions, including pet allergies. |
| rs9266227 | HLA-C | C | Increased risk for pet allergy. |
HLA and peanut allergy
Unlike many other allergies, peanut allergy can lead to a grade IV allergic reaction called anaphylaxis, which can be fatal if not treated in time.
Common symptoms of anaphylaxis include redness or swelling on the skin, runny nose, itching, tingling, and tightening around the mouth and throat.
Individuals may also experience digestive problems like diarrhea, and shortness of breath with wheezing.
| rsid | gene | risk allele | implications |
|---|---|---|---|
| rs7192 | HLA-DRA | G | Decreased risk for peanut allergy. |
| rs9275596 | HLA-DQB1 | T | Decreased risk for peanut allergy. |
The presence of the G allele on the SNP rs7192 of the HLA-DRA gene reduces the risk of developing a peanut allergy.
| rsid | risk allele | implications |
|---|---|---|
| rs7192 | G/G | Normal |
| rs7192 | G/T | 1.7x higher risk of developing peanut allergy. |
| rs7192 | T/T | 3x higher risk of developing peanut allergy |
Another SNP rs9275596 is associated with the increased susceptibility to develop peanut allergy in people of European descent.
The presence of the T allele is associated with the decreased risk of developing a peanut allergy.
| rsid | risk allele | implications |
|---|---|---|
| rs9275596 | T/T | Normal |
| rs9275596 | C/T | 1.7x higher risk of developing peanut allergy. |
| rs9275596 | C/C | 3x higher risk of developing peanut allergy. |
HLA and pollen allergy
Pollen allergy is basically the allergy to pollen that is shed by plants during the spring or summer seasons.
The symptoms of pollen allergy are similar to other allergies.
Presence of the T allele in SNP 2155219 increases one’s risk of developing hay fever and allergy to grass pollen.
Home remedies for allergies
While it is possible to avoid some of our known allergens, we still tend to encounter an allergic reaction every now and then.
Even though there are anti-allergic medicines such as antihistamines that can be taken to resolve an allergic reaction, many people prefer to use some natural home remedies.
Here is a list of home remedies which have proven to be effective in treating allergic reactions:
- Vitamin C: This vitamin is a natural antihistamine, antioxidant, and antitoxin.
- Honey: Raw honey is a natural allergy relief option.
- Mint: Mint can be used as mint essential oils or can be consumed as mint tea.
- Probiotics: They re-stock the good microbiota in our gut which promotes faster recovery.
- HEPA filters: HEPA filters and air filters can be used to limit pollen exposure.
- Spirulina: Consuming spirulina can alleviate the symptoms of hay fever.
- Stinging nettle: It is a natural antihistamine.
- Quercetin: Naturally found in broccoli and citrus fruits, it helps control the allergy symptoms.
- Essential oils: Peppermint or eucalyptus oil can be diffused into the air for some bronchial relief.
- Bromelain: Found in some fruits like papaya and pineapple, bromelain is known to reduce inflammation.
HLA antibodies
Antibodies are substances that are produced by the human body in response to foreign substances that enter the body.
HLA antibodies are also formed in pregnant women.
During blood transfusions and organ donation, these HLA antibodies are not harmful to the person producing it.
However, when there are HLA antibodies already present in the blood or plasma products that are transfused, it can create complications to the recipient.
This HLA antibodies-containing transfusion can lead to a serious complication called Transfusion-Related Acute Lung Injury.
This is characterized by a sudden acute respiratory distress post-transfusion.
A blood test can help detect the presence of HLA antibodies in one’s blood.
If you test positive for HLA antibodies, it poses no risk to you but you will not qualify for plasma or plasma blood products donation.
However, you can still donate your red blood cells.
