Why this person?
Two people sit at the same table.
They eat the same mustard dressing.
One notices that it tastes pleasantly sharp.
The other's immune system may respond as though something dangerous has entered the body.
The mustard proteins are the same.
So what is different?
This is one of the central mysteries of allergy.
There is no single "food allergy gene", no single environmental exposure and no single childhood event that neatly explains why one person develops food allergy and another does not.
Instead, current evidence points towards an interaction.
Genes influence susceptibility.
The condition of barriers such as the skin matters.
The route and timing by which the immune system encounters allergens may matter.
Microbes living in and on us may influence immune development.
The wider environment appears to matter.
And chance probably plays a role too.
To understand this properly, we first need to meet a word that appears repeatedly in allergy medicine:
atopy.
Atopy: an immune system with a particular tendency
Some people have an inherited tendency to develop conditions involving allergic sensitisation.
That tendency is called atopy.
Atopic conditions include:
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atopic eczema;
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allergic rhinitis, including hay fever;
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allergic asthma;
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and some forms of food allergy.
This does not mean somebody with hay fever will inevitably develop food allergy.
Nor does it mean that everybody with food allergy has asthma or eczema.
It means these conditions occur together more often than chance alone would predict because they share underlying biological tendencies.
Family history therefore matters.
A child with parents or siblings who have allergic disease has an increased likelihood of developing allergic disease themselves.
But genetics are not destiny.
Identical twins share essentially the same genome and can still differ in their allergies.
And the apparent increase in allergic disease over recent decades has happened far too quickly to be explained by large changes in human genes.
Genes load part of the dice.
Something else influences how they fall.
The skin is much more than wrapping
For a long time, skin was easy to think of as biological packaging.
It kept our insides in and the outside world out.
Modern immunology has revealed something far more interesting.
The skin is an active immune organ.
It contains immune cells, produces signalling molecules and constantly interacts with the environment.
And one of its most important jobs is to act as a barrier.
A useful analogy is a brick wall.
The skin cells are the bricks.
Proteins and lipids helping seal the spaces between them act rather like the mortar.
A healthy wall makes it difficult for unwanted material to pass through.
In eczema, that barrier can become impaired.
The mortar is less effective.
Water escapes more readily, contributing to dry skin, and substances from the environment can gain greater access to the immune system beneath.
That turns out to be extremely important to food allergy.
The extraordinary story of filaggrin
One of the most illuminating discoveries involves a protein called filaggrin.
Filaggrin contributes to the structure and barrier function of the outer skin.
Certain variants in the gene encoding filaggrin — FLG — can impair that barrier and are strongly associated with atopic eczema.
Research has also linked filaggrin loss-of-function variants with food sensitisation and food allergy.
This does not mean there is a simple genetic test saying:
You have this FLG variant, therefore you will become allergic to mustard.
There isn't.
The importance of filaggrin is conceptual.
It demonstrates that a defect in the physical barrier separating the immune system from the environment can influence allergic disease.
Suddenly, eczema isn't merely an itchy rash occurring alongside food allergy.
In some people, damaged skin may be part of the route by which food sensitisation develops.
How does food get onto a baby's skin?
At first, this sounds peculiar.
Why would a baby's skin ever encounter peanut, egg — or potentially mustard — before the child eats it?
Because food proteins don't remain politely on dinner plates.
Adults cook.
People eat.
Hands touch surfaces.
Food particles enter household dust.
Creams and cosmetics can contain food-derived ingredients.
Older siblings eat nearby.
Tiny quantities of proteins can move around the domestic environment.
Research has detected food allergens in household dust and explored associations between environmental exposure and sensitisation, particularly where the skin barrier is impaired.
Now imagine a baby with significant eczema.
The immune system may encounter food proteins through inflamed, permeable skin before — or alongside — encountering them normally through the gut.
That observation helped inspire one of the most influential modern theories of food allergy.
The dual-allergen exposure hypothesis
The dual-allergen exposure hypothesis proposes, in simplified form, that the route of early allergen exposure can influence whether the immune system learns allergy or tolerance.
Exposure to food proteins through damaged skin may promote sensitisation.
Eating those proteins through the gastrointestinal tract at an appropriate developmental stage may promote oral tolerance.
Think of the developing immune system as learning context.
Food arriving through the digestive system is appearing where food is supposed to appear.
The gut has evolved elaborate mechanisms for tolerating enormous quantities of harmless foreign proteins because otherwise every meal would become an inflammatory event.
Food protein entering through damaged skin arrives in a very different immunological environment — one potentially already signalling injury and inflammation.
The immune system may therefore receive different lessons from the same protein depending on where and how it first encounters it.
This is a simplification of extraordinarily complicated biology.
But it helped generate a hypothesis that could actually be tested.
And peanut provided the famous test.
The study that turned allergy advice upside down
For years, avoidance seemed intuitively sensible.
If peanuts cause allergy, perhaps delaying peanuts would prevent allergy.
High-risk babies were therefore often kept away from allergenic foods.
Then researchers noticed something intriguing.
Jewish children living in Israel appeared to have much lower rates of peanut allergy than Jewish children in the UK, despite related genetic backgrounds.
One striking dietary difference was that Israeli infants commonly ate a peanut-containing snack called Bamba from an early age.
Could eating peanut early actually protect against peanut allergy?
The landmark LEAP trial — Learning Early About Peanut Allergy — tested that idea in infants at high risk because they had severe eczema, egg allergy or both.
The results, published in 2015, were remarkable.
Among eligible infants who initially had no evidence of peanut sensitisation on the study's skin test, peanut allergy by age five developed in approximately 13.7% of those assigned to avoid peanut, compared with about 1.9% of those assigned to consume it.
Among a second group who began with a small positive skin test, the corresponding figures were approximately 35.3% with avoidance and 10.6% with consumption.
Early peanut consumption had dramatically reduced peanut allergy in this selected high-risk population.
The old intuition — avoid the allergen to prevent the allergy — had been challenged by a randomised controlled trial.
That changed infant-feeding guidance around the world.
This does not mean "feed babies allergens as early as possible"
Important research is particularly vulnerable to being converted into oversimplified slogans.
LEAP did not prove that parents should randomly feed every conceivable allergen to every newborn.
It studied peanut.
It involved infants of specified ages and risk characteristics.
High-risk infants were assessed before introduction.
The food was given in an age-appropriate form.
And peanut was then consumed regularly.
Research involving other allergenic foods has produced a more complicated picture, and recommendations have evolved as the evidence has developed.
Current UK advice generally supports introducing common allergenic foods from around six months, one at a time and in age-appropriate forms, without unnecessarily delaying them once complementary feeding begins. Babies with eczema or an existing food allergy may need individual advice because they are at higher risk.
What it emphatically does not establish is:
"To prevent mustard allergy, give babies mustard."
We do not have equivalent prevention evidence for mustard.
Extrapolating from one allergen to another without evidence is precisely what an authoritative resource should avoid.
Why mustard cannot simply borrow peanut's evidence
Peanut and mustard share some interesting biological features.
Both are seeds.
Both contain stable seed-storage proteins.
Both can produce IgE-mediated reactions.
But they are not interchangeable research subjects.
Prevalence differs.
Patterns of exposure differ.
The proteins differ.
Typical ages and routes of dietary introduction may differ.
And the evidence base for mustard prevention is tiny compared with peanut.
We can reasonably say that discoveries in peanut allergy have transformed our general understanding of oral tolerance and food-allergy prevention.
We cannot say that a particular mustard-feeding schedule has been proven to prevent mustard allergy.
There is no such established schedule.
This distinction — between biological plausibility and clinical evidence — is one of the most important habits in reading health research.
Something can make perfect scientific sense and still not yet have been shown to work in people.