Testing for allergen components – the allergenicity of molecules – Allergy Research Foundation meeting
Michelle Berriedale-Johnson reports on the Allergy Research Foundation meeting – in layman's language...
Most people who suffer from food allergies are aware that it is the protein in the food that causes the problem and, until relatively recently, most doctors would have gone along with that. But, as research progresses, as so often happens, the picture becomes more complex. Because, of course, proteins are themselves made up of a number of component molecules, each of which may differ from the other, and each of which may carry their own allergenicity. Dr Adriano Mari, Head of the Centre for Molecular Allergology in Rome and Dr George du Toit, consultant Pediatric Allergist at Guy's and St Thomas Hospital addressed the issue in the first two talks.
But it does not stop there. Many people will have heard of Fel d 1, the 'cat' allergen. But Fel d 1 is only one of an number of molecules to be found in cat allergen: there are also Fel d 2, 3 4 and 5. Although Fel d 1 triggers the most reactions, you can equally well be allergic to any of the others. Indeed, long-term cat allergen sufferers may remember the Allerca cat that was genetically modified to exclude Fel d 1, but no other molecule. As a result, many of those who shelled out thousands of dollars to buy an Allerca cat, found that they still reacted to it as they were allergic not just to Fel d 1 but to other molecules still carried by the Allerca cats.
And the same applies to foods. The allergic protein in a peanut is known as Ara H (from Arachis hypogaea) but there are many Ara H molecules (1 through to 9) and each behaves in a different way: 1 – 3 are heat resistant, 8 is relatively harmless, 9 is the most common etc. Only around 25% of peanut allergics react to only one of these molecules, most are what allergists call 'promiscuous' in that they react to several – although which will depend on the individual.
A single 'allergic' molecule may also share many characteristics with another 'allergic 'molecule in a different protein. For example, Gly M 4 (a molecule in soya) closely resembles Bet V 1 (a molecule in birch) so someone who is allergic to Bet V 1 could also have a crossover reaction to soya – see this research report from last month.
Moreover, if you are allergic to just one molecule, as long as it remains 'bound' into the food along with the other molecules, fats etc it may not trigger a reaction, but if 'revealed' by precessing of some kind you may react to it. Thus someone who is allergic to some of the allergenic components of hazelnuts may be able to eat Nutella without suffering a reactions as the component to which they would react is effectively buried within the other elements of the Nutella.
This research obviously, open the way to infinitely more accurate diagnosis – but, it requires that all the potentially allergenic components in each allergen (food, contact or inhaled) be identified. This is what Dr Mari's center is attempting to do, funding allowing, in their Allergeme project – a truly massive undertaking.
It also then requires an allergist to be able to detect the individual molecular allergenicity of each patient; ie which particular component or components in the allergen (peanut, cat etc) is the patient reacting to as opposed to just reacting to the whole peanut or cat. This would enormously increase our knowledge about and, hopefully, our ability to deal with allergens but it will be some time before it moves from the research laboratory into common clinical practice.
Oral Allergy Syndrome
Dr Du Toit also discussed the increase in Oral Allergy Syndrome (OAS) which he attributes largely to the increase in the numbers of birch trees which share allergenic components with many fruits. However, he commented that OAS rarely appears to develop into anaphylaxis.
Dr du Toit regards an oral food challenge as being the diagnostic gold standard and often advises it for those suffering from OAS as, if negative, it rules out anaphylaxis which can have a number of lifestyle implications for the patients such as their ability to get jobs, insurance etc.
He pointed out that children need to be regularly re-rested as their allergic profile will vary enormously according to their age. He also commented on the increased information that could be obtained on individuals' allergenicity via the ImmunoCAP ISAC test which gives reactions to over 100 components thereby allowing the allergist to identify sensitisation and cross reactivity patterns.
Idiopathic anaphylaxis and Hyper IgE syndrome
Dr Stephen Jolles from Cardiff University School of Medicine described the investigations that his team had made into 107 patients from five centres around the UK who had suffered from idiopathic or unexplained anaphylaxis. Using component testing they were able to discover reactive connections among the majority of the subjects, mainly to food allergens, which had not been revealed by previous allergen skin prick tests.
He also commented on the very rare condition, Hyper IgE Syndrome, the symptoms of which (coarsened skin, broadened nose, susceptibility to infection and to fractures) bear a close resemblance to those of very bad eczema which may well have confused diagnosis. However, it appears that this condition may not be allergy driven.
The meeting was organised by the Allergy Research Foundation in conjunction with the Allergy Academy who had hosted a morning session on Dermatology and Allergy.
First published in November 2011
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