Introduction

Allergies are a complex immune disorder that can be deadly if precautions are not taken. Allergies occur when the immune system detects an allergen and then the immune system reacts to it which is the cause for the symptoms. The symptoms can vary greatly and often involve groups of organs, but common symptoms include nausea (digestive system) and hives (integumentary system). If two or more organ systems are involved in an allergic reaction, it can escalate to anaphylaxis, a life threatening situation your blood pressure can drop and your airways can constrict. Luckily, allergies can be treated in multiple ways and the study of using proteomics to treat it is called allergenomics. Allergenomics focuses on targeting the direct protein that is causing this cell reaction and analyzes how the antigens change due to the environment and explores the causes of the allergy. It is still a relatively new idea so it will take some time to develop, but will lead to great results once developed.

Disease information

Allergies are a complex disease and therefore involve a lot of organs and because there are multiple types of allergies, there are also numerous symptoms.

• Clinical symptoms for food allergies
  • Itchy, watery, red swollen eyes
  • Nausea and Vomiting
  • abdominal pain and Cramping, Diarrhea
  • skin rash, hives, itching, blisters and skin peeling

Tests available

Skin testing also called patch testing - Your skin is pricked with a lot of different allergens as the allergens enter the body. There are normally around 10-20 things that they check for and is mainly done on your back. After 15-20 minutes, the doctor examines the back to see how each spot reacted to the specific allergen and based on this, the doctor can tell how much you are allergic (if you are) to each substance. If the spot is very itchy and swollen it normally means that you are very allergic to it.

Blood testing - Allergy blood tests are normally an alternative for those who cannot do skin testing. The blood tests look for higher levels of immunoglobulin in the blood to see whether your body is producing more antibodies than average

Spirometry (lung testing) - This type of allergy testing is mainly for asthma. It examines how asthma can affect the airways and the lung capacity by closely monitoring how the lungs are functioning

• Allergies are very common in today's society as almost ⅓ of the entire US population has them which means that treatment is extremely vital

Cycle of what happens during an allergic reaction that starts with the allergen and at the very end the allergen contacts the mast cell which creates a loop. (Source)

Types of treatment

Medications - There are multiple medications that a patient can take in the case of an allergy. This will prevent the allergy from spreading to the body and causing more symptoms but does not permanently get rid of it like immunotherapy. An example is epinephrine for peanut allergies and albuterol for asthma. (epinephrine is over 99% effective)

Immunotherapy - Immunotherapy works by giving the patient an allergen in a controlled hospital setting and slowly increasing the dosage every time they visit. This will build up immunity against the allergen and eventually get rid of the allergy. It is safe because it is done in a hospital, with numerous doctors in case any step goes wrong. It also has a very high rate of success: 80-90%

ALLERGENOMICS - Allergenomics is the use of proteomics to find solutions towards allergies. It looks at the exact protein that signals the immunoglobulin and uses existing knowledge of immunology and proteomics to find solutions

• Clinical trials (are available in multiple big organizations):
• Ex: 15 clinical trials available at mayo clinic

To start the process of allergenomics, proteins are removed from an allergen. These proteins are then viewed through gel electrophoresis as seen in the image (Source)

Gene level info

Allergenomics investigates how specific proteins within allergens can trigger the production of antibodies in the immune system and ways to target these proteins. Allergic reactions are not solely dependent on the allergen itself; they involve a complex interplay. Certain proteins serve as signals that prompt immune cells to generate antibodies, thus mediating the allergic response. An example of a crucial protein in this process is ESET1, which plays a significant role in regulating specific immune cells, such as CD4 and T helper cells. These immune cells are essential in orchestrating and coordinating the overall immune response during allergic reactions.

In addition to protein influences on allergy development, there is a hereditary connection to allergies. The likelihood of children developing allergies is partially determined by their parents. If both parents have allergies, the chances of the child having allergies increase significantly to 75%. However, other factors also contribute to allergy development, as demonstrated by Genome-Wide Association (GWA) studies. Notably, one strong genetic locus associated with allergy sensitization, supported by GWA studies, is found on chromosome 11q13. Furthermore, these studies revealed that nine out of ten loci related to allergic sensitization were also associated with asthma in a separate study.

This image displays the histamine releasing from the mast cells after the IgEs attach

Moreover, specific genes are susceptible to mutations, Single Nucleotide Polymorphisms (SNPs), or minor changes that can lead to the development of allergies. These genes include TLR6, C11/f30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2, and HLA-B. Individuals with allergies often exhibit minor changes at ten specific genomic sites, where one DNA block has been substituted with another. These alterations were not observed in the control group without allergies.

Research

There are numerous studies that cover multiple aspects of food allergies and allergenomics however we will focus on 2 main ones

1. Diagnosis and management of food allergy
2. IgE-Mediated Peanut Allergy: Current and Novel Predictive Biomarkers for Clinical Phenotypes Using Multi-Omics Approaches

Model

Allergen Exposure

Steps

1. The allergen attaches to immunoglobulin on the B cell
2. The B cell starts created IgE and spreads it to other immune cells to signal that an allergen has invaded
3. Mast cells pick up the IgE's and then get sensitized once allergens go to IgE's
4. This interaction prompts the mast cells to release histamine (cause of symptoms)
5. The release of histamine can lead to anaphylaxis, a life threatening situation if not handled correctly

Future directions

Allergies and allergenomics

I think that expanding allergenomics is a beneficial idea because targeting the exact protein that causes the allergy will lead to long term benefits. It can help solve a lot of people's lives and improve the quality of life for those with allergies if drugs are developed that only direct focus on the causing proteins. As of now, there is a lot of money being spent on allergy research, but I think some of that money should be dedicated to allergenomics and advancing in this sector. Allergenomics will progress very far with more funding and it will have a long term impact.

Next set of experiments

There should be a clear plan that maps out the next set of experiments. To begin, research funds should be spent testing different drugs that target the protein in charge of signaling the immunoglobulin to attack (ETS1). Finding a way to shut off this protein or prevent it from signaling immunoglobulin when allergens enter will solve the bigger part of this problem. Once a drug is made, it should be tested on animals such as mice and if this is proven to be effective multiple times, then there should be different groups of humans that volunteer for a clinical trial. In addition to drugs that target the protein, there should also be drugs that can prevent immunoglobulin from attacking specific proteins that lead to the release of histamine.

Cells' roles during an allergic reaction, with T cells, B cells, and the Mast cells. (Source)

Conclusion

Research is constantly evolving and now we have reached the point where we can look further into allergies and their causes using past omics such as proteomics and even advance further into immunology. We have progressed a lot in the past couple of decades in terms of advanced technology, but there is still a lot to be done. More than 100 million people suffer from allergies in the US each year and that is about ⅓ of the population. This means it is extremely vital to find a more permanent solution that is guaranteed to work and doesn't not span over such a long time like immunotherapy which is the only proven permanent treatment. That is when allergenomics comes in hand. Being able to understand in depth what role proteins play in allergies can help us invent medicines that target only specific proteins and help people live without allergies. In the US, there are around 30,000 hospitalizations due to allergies and 150-200 deaths per year. But it is not only the lives, allergies can prohibit people from living their best life because they always have to be cautious. The money we spend on allergenomics is reversible but the lives we lose without it are not.

Looking at a proteomics approach to study apple allergenicity, there are multiple peptides that can be specific and unspecific and these link to isoforms that can mark the different allergens. For example, certain peptides in CBL94177.1 isoform made apples hypoallergenic. Two other isoforms, CBL94148.1 and XP_008346874.1 can make patients less susceptible to apple allergies. These can be tested using skin and patch tests as explained on the first page. The information we learn from studies like these are crucial for advancing in immunology and allergenomics. In conclusion, certain peptides and isoforms can make a patient at higher risk to an allergy or at lower risk and this depends on which proteins are present in the cell. Using this information to identify which proteins can make allergies escalate is the best utilization of allergenomics.

References

1. Identification of allergenomic signatures in allergic and well-tolerated apple genotypes using LC-MS/MS - ScienceDirect

2. https://sciencenordic.com/allergies-asthma-biotechnology/allergy-genes-identified/1388080

3. Allergies Clinical Trials - Mayo Clinic Research

4. Why Are Some Proteins Allergens? | Toxicological Sciences | Oxford Academic

5. Genetics of allergy and allergic sensitization: common variants, rare mutations - PMC

6. https://aafa.org/asthma-allergy-research/our-research/

7. https://www.foodallergy.org/research-and-innovation.

8. (PDF) Proteomic applications in food allergy: food allergenomics | Isabella Lante and Maurizio Muraca - Academia.edu

9. Penn Research Shows How Genes Make Us Prone to Allergies

10. Are Allergies Inherited?

11. Genetics of allergy and allergic sensitization: common variants, rare mutations - PMC

12. Allergenomics (Rapid and Comprehensive Analysis of Putative Allergens)

13. Genetics of Food allergy - PMC

14. IgE-Mediated Peanut Allergy: Current and Novel Predictive Biomarkers for Clinical Phenotypes Using Multi-Omics Approaches - PMC

15. Diagnosis and management of food allergy - PMC

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_By: Rachna Chinya_

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of Elio Academy.