Understanding the molecular basis for food-allergic reactions

Eight foods account for 90percent of all reactions in the USA: milk, eggs, peanuts, tree nuts such as walnuts and pistachios, wheat, soy, fish, and shellfish such as lobster and shrimp.

Food-allergic reactions result in over 30000 visits to casualty departments every year, with between 150and 200people dying annually in the country from anaphylactic shock.

So what are the hot topics of research interest? The latest announcement from the Food Allergy and Anaphylaxis Network (FAAN) gives a good idea. This non-profit organisation works for the 11 million Americans with food allergies and has just selected the first five scientific research studies for its newly established research grants programme.

The studies cover the breadth of food allergy research. For example, a pilot study at Duke University is to test oral immunotherapy in patients allergic to peanuts. The aim here is to create a new treatment that lowers the risk of anaphylactic reaction and changes the peanut-specific immune response.

An investigation at the University of Cincinnati medical centre will try and determine why food allergens cause some people to develop life-threatening systemic anaphylaxis while others develop gastrointestinal symptoms that are painful and disabling, but not life-threatening.

At Virginia Commonwealth University, scientists hope to develop a novel system to test different compounds that will recognise peanut-specific allergens and aturn-off' the cells that play a major role in an allergic reaction.

Meanwhile an investigation at Cincinnati's children's hospital medical centre into eosinophilic oesophagitis, a type of immunoglobulin (Ig) G-mediated allergy, should lead to a better understand of the condition and gather insight into diagnosis and treatment for this type of food allergy.

The last project is being run by the Mayo Clinic and follows up an earlier population-based study on the epidemiology of anaphylaxis in Olmsted County. This data will then be used to estimate nationwide statistics.

More than US$700000 was awarded in the inaugural round of research grants, much of it raised by FAAN members.

“In the past 10 years, scientists have learned significantly more about food allergies. Just 10years ago, it was believed that only one per cent of the American population was food allergic. Through sound scientific research, we now know that four per cent or 1-in-25 Americans have food allergies,“ explained Anne Muñoz-Furlong, FAAN's founder and ceo.

Also in the USA, the Food Allergy Research and Resource Programme (FARRP) is developing assays to detect allergenic food residues that might contaminate other foods. Currently, FARRP's research is focused on immunoassays ­ specifically, enzyme-linked immunosorbent assays (Elisas).

In the FARRP Elisa format, antisera are developed using crude extracts of allergenic foods or specific proteins from allergenic foods as the antigens.

IgG antibodies against certain proteins in the crude extracts are produced. While the IgG antibodies may be directed at proteins that are not allergens, FARRP believes that the detection of any protein or group of protein from the allergenic food signifies the presence of the allergenic proteins.

So the FARRP Elisas detect residues of allergenic foods rather than food allergens. Nevertheless, the organisation says that these Elisas are quite useful for detecting allergenic food residues arising from such food industry practices as using shared processing equipment or using rework.

The organisation already has Elisas available for the most commonly-allergenic foods in the USA, including almond, egg, milk, peanut, whey and walnut. A kit for experimental purposes is available for soy, while Elisas for cashew, clam, hazelnut, pecan, sesame and shrimp and currently under development.

Why is an allergen an allergen?

In Europe, one of the most interesting research projects is focusing on the unpredictable distribution of allergens in plants. For example, being allergic to birch pollen can predispose a person to allergy from distantly related plant foods such as celery, apple or soy.

Most allergens are proteins and newly published research identifies 129plant allergens in just four main protein families.

“Knowing what makes a protein more likely to become an allergen could make it easier for manufacturers to identify potential allergens in novel foods and ingredients, preventing them from reaching the consumer,“ said Clare Mills, head of the allergy research team at the UK's Institute of Food Research (IFR).

Proteins are constructed from amino acids, and previous research has focused on analysing the sequence of amino acids to identify potential allergens. However, this can lead to false predictions. Sequence data alone does not reveal how amino acids interact to construct proteins. The interaction of amino acids creates proteins folded into particular shapes. The new research by a team of scientists considered both amino acid sequence and structural similarities between surface features of plant proteins using a 3D computer model(Fig.1).

“By modelling surface features of proteins from a range of flowering plants, we were able to explain why cross-reactions can occur between species that otherwise seem dissimilar,“ said Mills. “This is especially important to help us understand why people with allergy to birch pollen can suffer related allergies to fresh fruits and vegetables.“

Flowering plants first appeared over 100million years ago during the late Jurassic period, the age of the dinosaurs. They became the most dominant plant on Earth and today include all our food plants. Very early in their evolution there was a split into two major groups. Some plant protein structures changed and some stayed the same, or were conserved.

“We found that even a single conserved region on the surface structure of a protein can cause cross-reactivity,“ said Heimo Breiteneder of the Medical University of Vienna.

Scientists had already observed that although humans consume an enormous diversity of plant foods, just a few foods account for the majority of food allergies. However, their relatedness remained unclear. For the first time, the distribution of plant food allergens has been measured according to protein families. The scientists found that 129 allergens could be classified into just 20out of 3849 possible protein families, with just four super families accounting for more than 65percent of food allergens.

“We are only now in a position to begin to understand what makes an allergen an allergen,“ added Breiteneder.

And that opens a whole new area of work. For example, whilst peanuts are a major allergen, their close botanical brothers peas pose little threat. And although peanuts and tree nuts are not related ­ peanuts are classified as legumes ­ cross-reactions occur. This remains a mystery, but is under investigation at IFR.

The research, published in the Journal of Allergy and Clinical Immunology, was funded through the Biotechnology and Biological Sciences Research Council (BBSRC) competitive strategic grant to IFR and Rothamsted Research with additional support from the EU.

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