To understand why peanut allergies can be so severe, it helps to start with what a peanut actually is. It can help to think of a peanut as not just one thing, but as a collection of different proteins, each with its own structure, its own stability level, and its own relationship with the immune system. When your body reacts to a peanut, it isn't reacting to 'peanut' as a single substance; it's reacting to one or more specific proteins that your immune system has learned to identify as threats. Understanding these specific proteins helps clinicians gauge how severe a reaction might be, and guides research into future allergy treatments. Here we’re looking at what’s actually happening inside a peanut when someone with an allergy encounters one.
What are seed storage proteins and why do they matter?
Peanuts are very chemically dense. They evolved to pack as much nutritional resource as possible into a small structure that can survive until conditions for germination are right. Seed storage proteins are what allow this. They are large, stable protein complexes that survive digestion unusually well compared to many other food proteins. This stability, which evolved to protect the seed, turns out to be one of the main reasons peanut allergens are so potent and can cause reactions in small amounts and long after digestion. A protein that resists breaking down in the soil, also resists breakdown in the human digestive system. This means it survives long enough to be encountered by the immune system in its intact form. The same thing that makes peanuts a nutritious food, makes their proteins difficult to neutralise and break down in the gut.
Seed storage proteins exist in high concentrations in seeds to provide a store of amino acids for the growing seedling. In peanuts, Ara h 1, Ara h 2, and Ara h 3 make up 75% - 90% of the total protein content [1]. There are at least 16 distinct peanut allergens (Ara h proteins) officially identified and recognised, so we won’t cover all of them.
Ara h 1 - the most abundant peanut protein
Ara h 1 forms stable trimeric complexes which means three protein units locked together. It's one of the most abundant proteins in the peanut, recognised by IgE antibodies in the majority of people with peanut allergies. This recognition means the body is trained to have an immune response when it detects Ara h 1, resulting in an allergic reaction.
The 'locking' structure makes it resistant to digestion. Roasting peanuts, which you might think destroys this structure and therefore reduces allergic reactions, actually increases allergenicity by causing structural changes that expose additional IgE binding sites. This is part of why roasted peanuts are often associated with stronger allergic responses than raw peanuts. The processing that makes them taste nicer, also makes their proteins more accessible for the immune system. Ara h 1 is a significant allergen, but it still isn’t the most potent.
Ara h 2 - the peanut protein that matters most
Ara h 2 is an allergen for over 90% of peanut-allergic patients and is considered the most widely potent peanut allergen [2]. It is structurally different from Ara h 1 - it is a small, tightly coiled protein held together by multiple strong chemical bonds. These bonds make it extremely stable, it resists gastric acid and digestive enzymes. Fragments of Ara h 2 have been found in the bloodstream and breast milk of people without a peanut allergy, meaning it survives the full journey through the digestive system basically intact, and then enters circulation. This helps explain why even tiny quantities (traces) of peanut protein can trigger reactions in highly sensitive individuals. The protein reaches mast cells throughout the body before it has a chance to be broken down.
There is also a structural feature unique to Ara h 2, where parts of the protein become hydroxylated. This hydroxylation significantly increases IgE binding activity, and is thought to be one of the reasons Ara h 2 is so disproportionately potent compared to other peanut proteins. Increased binding activity means a more severe allergic reaction. If someone has a blood test and finds Ara h 2-specific IgE is elevated, that result carries more clinical weight than sensitisation to Ara h 1 or Ara h 3 alone.
In specific tests called assays, Ara h 2 is approximately 100X more potent on a weight basis than Ara h 1 or Ara h 3 [3]. High levels of Ara h 2-specific IgE are associated with increased risk of severe reactions and anaphylaxis.
Ara h 3 - the Legumin
Ara h 3 is another unique protein, made up of six units assembled together. It shares approximately 66% of its sequence with glycinins found in soybean, which partly explains why some peanut-allergic individuals also react to soy. Its role in severe reactions is less pronounced than Ara h 2's.
Ara h 6 - the accomplice
Ara h 6, like Ara h 2, is a 2S albumin. Meaning, the two proteins share approximately 60% of their structure. Together, Ara h 2 and Ara h 6 account for the majority of the allergy effect potential of peanut extract. When both these proteins are removed, the peanut extract loses most of its ability to trigger anaphylaxis [4].
Ara h 6 has historically received less attention than Ara h 2 because most tests were developed around the three abundant proteins. But its clinical significance is increasingly recognised. Most people with peanut allergies become sensitive to both proteins at the same time, and the combined IgE response to Ara h 2 and Ara h 6 is a better predictor of clinical allergy than either alone. If testing has only reported Ara h 2 results, it's worth asking whether Ara h 6 was also measured. Overall, they are both the major peanut allergens.
Diagnosis and the future of treatment
Component-resolved diagnostics (CRD), known as molecular allergology and done via blood test, is testing for IgE antibodies against specific peanut proteins, rather than crude peanut extract as a whole. This has changed how allergists approach both diagnosis and assessing risk. Someone with more Ara h 2-specific IgE and a clinical history of severe reactions is in a different risk category to someone with only Ara h 8 sensitisation alone, which is typically associated with pollen-food allergy syndrome and milder oral symptoms. This type of testing can be offered via the NHS by allergy specialists, though must usually be asked for directly in many cases.
The distinction matters for whether an adrenaline autoinjector is prescribed, what avoidance advice is given, and who is considered a candidate for oral immunotherapy (OIT). The emergence of OIT, which works by exposing the patient to increasing doses of peanut protein under clinical supervision, is also rooted in this protein understanding. The treatment works partly by shifting the immune response away from the Ara h 2 and 6. Understanding which allergy proteins the immune system reacts to is no longer just scientific research. It's becoming the basis for personalised allergy management.
There is still a lot of ongoing research into the role of different peanut proteins. Researchers are looking at whether hypoallergenic peanut variants, that have genetically reduced expressions of Ara h 2 and Ara h 3, could eventually be developed for use in food production or as safer options for immunotherapy.
The old model of allergy management treated peanut allergy as a single condition with a single rule: avoid peanuts and carry adrenaline. What we now understand is more precise than that. Different proteins carry different levels of risk, and testing can increasingly reflect that reality. The more we understand about which proteins are responsible and why, the more accurately we can predict who is at risk of anaphylaxis, who might safely tolerate certain preparations, and what treatment might eventually look like.
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