Food allergies linked to animals' proximity to humans, says study

Scientists have found that the evolutionary distance of animal proteins to human proteins determines how likely they are to trigger a food allergy - research that could help with the development of free-from foods and allergy therapies.

The most common forms of food allergies in infants are cow's milk and hen's eggs.

For adults, fish and seafood are the most common allergens.

Researchers led by Dr Clare Mills of the Institute of Food Research in Norwich, UK, used sequence-based homology methods to classify food allergens into families.

They then performed in silico analyses to identify putative relationships in protein sequence, structure and allergenic properties.

"Overall we found that only an animal food protein that is less than 54 per cent identical to a human equivalent could become allergenic," said Mills.

In practical terms, she said this explains why people with a cow's milk allergy can often tolerate mare's milk, but not goat's milk, for instance.

Proteins in horse milk can be as much as 66 per cent identical to human milk proteins, while known allergens from cows and goats are all less than 53 per cent identical to their corresponding human proteins.

Mills and her co-researchers also found that most of the major animal-derived food allergens can be classified into one of three protein families: tropomyosins; EF-hand proteins; and caseins.

Amongst the tropomyosins - proteins found in muscle tissue and deemed the most important family - they found a link between allergenicity and class of the animal from which it originates.

"Tropomyosins in mammals, fish and birds are at least 90 per cent identical to at least one human tropomyosin and none have been reported to be allergenic," said co-researcher Dr Heimo Breiteneder of the Medical University of Vienna.

"In contrast, the allergenic tropomyosins are all from invertebrates such as insects, crustaceans and nematodes and at most are only 55 per cent identical to the closest human homologue."

Next came the EF-hand proteins.

The researchers found that those in birds and mammals are not allergenic to humans, while those in frogs and fish can be.

The third animal food allergen family, caseins, are all proteins from the milk of mammals.

The researchers looked at milk from rabbits, rats and camels as well as sheep, goats, cows and horses.

"Animal food proteins lie at the limits of the capability of the human immune system to discriminate between foreign and self proteins" , said Mills.

She explained that immune responses to some animal food allergens, such as the invertebrate tropomyosins, are almost a form of autoimmune response.

This has a bearing on the potential for developing unanticipated autoimmune responses, especially in the development of recombinant allergens for immunotherapy.

Last autumn researchers from Amsterdam reported at the BA Festival of Science in Norwich that promising work is underway to develop a vaccine against food allergies, and that this could be available in as little as ten years.

According to Dr Ronald van Ree of Amsterdam University new techniques in genetic engineering are being explored to reduce the effect of allergenic proteins.

The aim is to make these molecules safe enough to use in drugs that combat food allergies via the immune system.

In addition to the three main animal protein families, 14 small families consisting of up to three proteins were also identified by Mills' team.

The same team from Norwich and Vienna has previously conducted similar research on plant-derived allergens.

In that case, they found that there are a restricted number of protein families, too.

But in contrast with plant food allergens, it is only animal proteins that have been seen to challenge the capability of the human immune system to discriminate between foreign and self-proteins.

According to market analyst Mintel the overall 'free-from' market has already enjoyed sales growth of over 300 per cent since 2000.

The growing demand has opened up a new lucrative sector that many food makers are keen to exploit.

The term free-from includes a broad umbrella of allergens, but also elements that are thought to trigger an intolerance in some people rather than a full-blown allergy, such as wheat and lactose.

Source: The Journal of Allergy and Clinical Immunology DOI: 10.1016/j.jaci.2007.08.019 Title: Evolutionary distance from human homologues reflects allergenicity of animal food proteins.

Authors: John Jenkins, Heimo Breiteneder, Clare Mills