Recent advances in food allergy, 2016

MJC Alcocer, SC Ares, I López-Calleja

Recent advances in food allergy
Brazilian Journal of Food Technology, 2016


Food allergy is a public health issue that has significantly increased worldwide in the past decade, affecting consumers’ quality of life and making increasing demands on health service resources. Despite recent advances in many areas of diagnosis and treatment, our general knowledge of the basic mechanisms of the disease remain limited i.e., not at pace with the exponential number of new cases and the explosion of new technologies. Many important key questions remain: What defines a major allergen? Why do some individuals develop food allergies and others do not? Which are the environmental factors? Could the environmental factors be monitored through epigenetics or modified by changes in the microbiome? Can tolerance to food be induced? Why are some foods more likely to trigger allergies than others? Does the route and timing of exposure have any role on sensitization? These and many other related questions remain unanswered. In this short review some of these topics are addressed in the light of recent advances in the area.

New challenges and future

Recent reports from both Australia and the United States suggest that vitamin D might play a role in the recent increase in food allergy. Using indirect markers of food allergy status the results suggest that the further the patients reside from the equator, i.e. lowest ambient UV radiation, the more likely they will suffer from food allergy. Vitamin D levels are known to be associated with atopic disease development and the association of food allergy with latitude is most likely restricted to IgE-mediated mechanisms (OSBORNE et al., 2012). The existent data however, are controversial. In preliminary studies Vitamin D deficiency was associated with higher levels of IgE sensitization in children and adolescents (SHARIEF et al., 2011). However later studies demonstrated that high vitamin D levels in pregnancy and at birth may contribute to a higher risk for food allergy and therefore argues against vitamin D supplementation to protect against allergy (WEISSE et al., 2013).

Regarding treatment, the last few years have witnessed interesting new ideas on oral, subcutaneous and epicutaneous desensitisation using a plethora of methods such as anti IgE antibodies (omalizumab), herbal therapy, chimeric allergen-IgG, Fcε blockage, lymph node injection and patch therapy amongst others (SICHERER; SAMPSON 2014). Some are now in clinical trial phase II, others have just gone through the feasibilities studies. Although interesting and promising, the actual validation of the efficacy in humans still remains to be demonstrated. In the area of tolerance some interesting progress has been reported on the acceleration of the resolution of cows’s milk and egg allergy in children, by increasing dietary baked allergen intake (KIM et al., 2011; LEONARD et al., 2012). The results from these controlled studies suggest that simple measures are better than complete avoidance. On the same desensitisation route, the group in Addenbrooke in Cambridge have successfully induced desensitization in children with different degrees of severity to peanut allergy. The peanut Oral Immune therapy (OIT) used was able to raise the reactive threshold to at least 25 times, and in some cases almost 90% of the participants could tolerate the daily ingestion of up to 800 mg protein (ANAGNOSTOU et al., 2014). A recent development widely discussed in the 2015 EAACI meeting refers to the use of epicutaneous immunotherapy (EPIT). French and American groups have shown that epicutaneous but not oral immunotherapy induced the generation of gastrointestinal-homing antigen-specific Tregs in the skin-draining lymph nodes, which translates into an increased number of Tregs in the gastrointestinal tract. The induction of gastrointestinal Tregs is associated with an enhanced protection of mice from food-induced anaphylaxis by EPIT (TORDESILLAS et al., 2015). Some work, not yet published in humans, has also been discussed. The recent EPIT findings suggest the skin as a potent modulator of the allergic responses. This is interesting as in earlier work (2001-2003) the UK Avon Longitudinal study involving c.a. 14 000 families showed there was a possible link between the development of allergy to peanut and the use of creams on the skin to treat eczema. These findings and the recently reported cases of wheat-dependent exercise induced anaphylaxis patients sensitised to hydrolysed wheat protein in facial soap in Japan (HIRAGUN et al., 2013), corroborate the skin as a potent modulator of allergic responses. Whether these responses could be exacerbated by the presence of lipids or surfactants and NKT involvement or suppressed by induction of T regs as in the EPIT system, remain to be demonstrated.

Regarding the timing and selection of specific complementary foods, many studies continue to suggest that prolonged avoidance of solids or specific allergens is not protective and might be a risk factor with regard to atopy or food allergy prevention (SICHERER; SAMPSON, 2014). In this regard one of the most interesting developments regarding the natural induction of tolerance is the recent findings by the Learning Early about Peanut Allergy (LEAP) study (DU TOIT et al., 2015). Peanut allergy develops early in life and as described above it is rarely outgrown. Clinical practice guidelines in the UK and USA recommended the exclusion of allergenic foods from the diets of infants at high risk for allergy and from the diets of their mothers during pregnancy and lactation. However, it was observed that the risk of the development of peanut allergy was 10 times as high among Jewish children in the United Kingdom as it was in Israeli children of similar ancestry. Furthermore it was noticed that in the UK infants do not consume peanut-based foods in their first year of life, whereas in Israel, peanut-based foods are usually introduced in the diet when the infants are approximately 7 months of age. This was the motivation behind the LEAP study aiming to determine whether an early introduction of peanuts would offer protection from developing peanut allergy. The initial findings of the LEAP study were impressive. The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among high-risk children when compared with peanut avoidance at the age of 60 months (DU TOIT et al., 2015). Although these are still initial results and many aspects of the study such as dosage and low/high risk-patients need to be worked out, this study has been pivotal in altering pre-conceived ideas. From the number of interim guidance and discussions prompted in a number of allergy related societies worldwide, one has an idea of the importance of these findings (FLEISCHER et al., 2015).

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