Food Allergen Immunotherapy: Current Status and Prospects for the Future

Food allergies are a growing problem, with one in twelve children having at least one allergy, commonly peanut, eggs, milk, wheat, soy, and shellfish. Despite the enormity of this problem, allergists have so far been unable to provide any pro-active treatments, apart from advising patients to avoid those foods and to keep an epi-pen nearby in case of anaphylaxis.  But there’s now some hope.  In this month’s issue of JACI, Dr. Wood surveys a slew of new therapies that aim to modify the immune system so that children can be desensitized to the foods they are allergic to (J Allergy Clin Immunol 2016; 137(4): 973-982). 

The classic approach of desensitizing patients to environmental allergens – like pollens or dander - through shots, has been tried before with food allergies. Although this approach was somewhat successful for a few children, the risks were far too high and it has largely been avoided.  Recently, oral immunotherapy – that is, ingesting really small amounts of the food, and increasing that dose of food, over the course of weeks – is coming into fashion.  Early research results suggest that this approach is effective but it is still far from coming to the clinic.

More recently, sublingual immunotherapy has been tried: small amounts of the food is allowed to sit under the tongue for two minutes and then swallowed.  This amount is slowly increased to help children become less sensitive.  Compared to oral immunotherapy, it’s safer, but it also seems to be less effective.

This has led people to think of other ways to desensitize allergic children to their foods. One way is percutaneous immunotherapy, in which a patch with the food allergen is applied to the skin.  While research is still early, it looks promising – although a lot of side effects like local redness or eczema at the site of the patch have been reported.

A lot of unknowns remain– how long should children be on immunotherapy?  What are the long term benefits … and risks?  How do we measure success? And should we also be using ‘adjunct therapies’ like the anti-IgE antibody omalizumab while trying this immunotherapy?  Currently, we don’t have many answers but, much to the relief of the 8% of children with food allergies, cutting edge research should hopefully change that very soon.

Prevention of Food Allergy

Children are afraid of a lot of things: the dark, strangers, and even the bogeyman.  But for more and more kids, ordinary foods, like peanuts, eggs, and milk, are becoming sources of fear.  Food allergies are becoming increasingly common in the developed world, and we don’t have a good explanation of why.  In this month’s issue of JACI, du Toit and his colleagues talk about the factors that lead to food allergies, and what can be done to prevent children from developing food allergies (J Allergy Clin Immunol 2016; 137(4): 998-1010). It’s clear that there are some risk factors that we just can’t change: male gender, a family history of food allergies, and even race can put children at a higher risk for developing food allergies.  But there are other things that we can possibly change.  Since children with eczema (atopic dermatitis) tend to have food allergies, there have been some discussion about whether preventing and controlling eczema by regularly applying moisturizers could help prevent food allergies.  Attendant to the link between high levels of aerosolized peanut dust and the development of peanut allergies, it has been suggested that, at least for peanuts, children may become sensitized through the skin and not the gut. Thus, it is possible that by keeping the skin barrier intact, we may be able to prevent peanut allergy.  Studies are still ongoing; if successful, these would be simple ways to stop food allergies in their tracks.

Another big hope has been that we can mitigate the development of food allergy by modifying the types of food that the mother takes while pregnant or lactating.  To date, these studies have been inconclusive.  Likewise, there is not much data on the efficacy, or even safety of, dietary interventions such as fatty acids, antioxidants, pre- and probiotics and vitamin supplementation.

The one glimmer of hope is that early introduction of common food allergens during infancy may be a pro-active approach.  Two major trials, LEAP (Learning Early About Peanut Allergy), and EAT (Enquiring About Tolerance) have suggested that introducing children to peanuts during infancy does not lead to food allergy, and may actually help to prevent them.

Food allergy is an enormous problem but new research on prevention may help to bring it under control, and make sure that children can have at least one less thing to be afraid of. 

Molecular and Cellular Mechanisms of Food Allergy and Food Tolerance

One may not believe it, but there is an entire universe in one's belly.  One's guts, in and of themselves, are over 300 square meters in surface area, and are home to thousands of different species of bacteria, as well as an immune system that is exquisitely tailored towards sensing, which of the 300 kilograms of food ingredients  that we ingest each year are safe, and which are unsafe.  So in this veritable universe of bowel, it is incredibly difficult to figure out what decides whether one becomes allergic or tolerant to food.

Chintharajah et al tackle this problem in this month’s issue of JACI (J Allergy Clin Immunol 2016; 137(4): 984-997).  They begin by surveying the types of immune cells that service our gut.  They highlight the central role of a specific type of immune cell called the dendritic cell, which lives in the walls of the small intestine (among other areas), in capturing the proteins in food particles, processing them, and then presenting them to other types of immune cells.  In certain circumstances, particular food proteins, chemical messengers from the gut, and the genetic makeup of immune cells can move the immune system into a pro-allergic state.  Perhaps just as important is the role of another type of immune cell, the regulatory T-cell, which ensures the proper balance of immune responses.  When these regulatory T-cells don’t work properly, the immune system can go into overdrive and become less likely to see food proteins as safe and tolerable.

Interestingly, a lot of other surprising factors that may lead to food allergies.  The microbiome is not limited to the gut. The skin has its own microbial ecology and skin breakdown and inflammation can alter the skin microbiome and allow sensitization to aerosolized food antigens such as peanut dust.  in addition,  the gut bacteria in children with food allergies are less diverse and have different levels of different types of bacteria compared to children without food allergies. 

All of these factors need to be taken into consideration when one tries to   modify the immune system to nudge it away from producing an allergic response.  There are ongoing studies trying to figure out how to desensitize allergic individuals to certain foods.  Knowing how these approaches alter the immune system will help take those techniques out of research centers and into the allergist’s office.