T07010: Allergic cross-reactivity in peanut allergy

Study Duration: October 1999 to February 2003

Contractor: King's College, London

Peanut allergy has become a major concern in westernised countries in the past two decades. In contrast to other food allergies, it is rarely outgrown in adolescence and the symptoms are often severe and can be life-threatening. People who are allergic to peanuts are frequently also sensitised to tree nuts, but are only rarely allergic to other legumes (peanuts are a member of the legume family of plants).

The project investigated cellular reactivities in individuals reacting to peanut and to other foods, and compared these with results from healthy control subjects. T cells (cells involved in generating an allergic response) were analysed and their reactivities to independent stimuli and to food antigens (including peanut, soy, hazelnut, brazil nut, lupin, and egg and milk antigens) assessed. The interaction between cells that present antigens to the immune system and T cells was also examined. Finally, serum levels of IgG antibodies to several foods (including peanut, brazil nut, soy and lupin) were analysed in order to establish a measure of antigen exposure in contrast to IgE antibody sensitisation.

A related experimental study involving rodents was conducted to establish if tolerance to peanut could be induced by oral administration (i.e. if peanut could act as a tolerogen). This study also aimed to determine whether administration of peanut to the mother during lactation could affect the immune status of the offspring.

For the first part of the study, human blood cells were cultured with food extracts and the responses of the cells analysed. Levels of IgG antibodies produced to several food samples were measured by analysis of serum using enzyme-linked immunosorbent assays (ELISAs).

For the experimental rodent studies, peanut was administered directly by gavage to non-pregnant animals and lactating dams.

One major observation of the project was that individuals allergic to peanut and other food antigens secrete lower levels of the cytokine, IL-10, that is involved in tolerance induction than non-atopic controls (cytokines are chemicals secreted by immune system cells). This might imply a general inefficiency in down-regulating food specific allergic responses in these individuals. Furthermore, peanut allergic individuals produced less interferon (IFN), but more IL-10 to soy than non-peanut allergic individuals and control subjects. This shows that the immunological reactions to peanut and soy, two closely related food allergens, can be different in the same individual.

In addition to secreting less IL-10, peanut allergic and food allergic individuals were found to produce less of the cytokine IL-12, which is thought to counteract allergic responses. Peanut allergic individuals also had significantly higher levels of the IgG1 subclass of peanut specific antibodies. This demonstrates that antibodies can cross-react between botanically related foods without clinical symptoms.

The project also found that monocytes and B cells, which are cells involved in presenting food proteins to the immune system, are present in different numbers among food allergic individuals.

The experiments in rodents revealed that tolerance to peanut could indeed be induced by oral administration. However, the dose required to induce suppression was far higher than the dose of another common allergen (the egg allergen ovalbumin) that is required to induce suppression. In addition, the results of this preliminary study indicated that transfer of food antigen during lactation does have an effect on the immune response of the offspring. It was found that peanut protein administration to offspring via lactation during a limited period (14-18 days after birth), could sensitise the offspring to antigens transmitted via this route.

The researchers concluded that peanut allergic individuals have a different cytokine secretion pattern to non-tolerated foods than control subjects, and that this different cytokine secretion pattern is likely to involve antigen presenting cells. The researchers hypothesise that a skewed population of antigen presenting cells might facilitate the spreading of sensitisation to other foods. Therefore, they suggest that any intervention that is likely to be successful in food allergy should involve these cells. However, further work is needed using younger individuals where the process of allergy development is still ongoing in order to confirm the findings.

With regard to the experimental work in mice, the researchers conclude that tolerance induction to peanut requires higher doses of antigen than is necessary for other food allergens, and that levels normally associated with tolerance induction may sensitise. They postulate that a reason for the clinical observation that peanut allergic infants may react to their first known exposure could be due to immunological programming sensitisation via breast milk in susceptible individuals.

Final report is available from the FSA Library and Information centre.
To obtain a copy, please contact the Enquiry Desk, Dr. Elsie Widdowson Library and Information Services, Food Standards Agency (020 7276 8181/8182 or at library&info@foodstandards.gsi.gov.uk).

Contact: For any enquiries concerning this research project, please contact the relevant Programme contact or email science@foodstandards.gsi.gov.uk