By Kari Nadeau, MD, PhD, FAAAAI
I don’t have to tell readers of this website about the heartbreak and anxiety of food allergies. The Lucile Packard Children’s Hospital at Stanford houses the Stanford Alliance for Food Allergy Research (SAFAR) the only research center on the West Coast conducting oral immunotherapy (OIT) trials, often in concert with other centers east of the Rockies. We are the focal point for the hopes of thousands of children and families for relief from this evolutionary mistake, this maladaptation, in which the body’s own immune system turns against us. My colleagues and I take these hopes very seriously.
The demographics of food allergy ought to alarm anyone concerned with the health of future generations. Food allergies are emerging in alarming numbers of children under three. While many of their elders might continue to dismiss them as marginal “nuisance” diseases that can only be managed, not cured, children’s food allergies, like other chronic illnesses, have life-long behavioral and learning consequences as well as physical ones. When the clock starts ticking at age three, the cost in quality of life can be high.
The SAFAR network of physicians and scientists is working across multiple disciplines to achieve what we all hope for most: a cure. Our current research is promising! The families who turn to us for treatment of food allergies and related disorders every year offer the unique opportunity for research and clinical studies that could lead to new insights and the development of novel therapies. We are carrying out clinical food immunotolerance studies, including oral immunotherapy for milk and peanut allergies and research in eosinophilic esophagitis, a commonly associated inflammatory disorder of the esophagus.
We are also the only center in the country to offer clinical research studies to patients with multiple food allergies. For example, in the spring of 2009, we conducted a study using a course of treatment I developed in immunotolerance, where individuals with severe food allergies consume minute doses of the allergens, and then gradually increase the dosage as they build tolerance. This study included 21 children between the ages of 6 and 13.
Today, every one of the study participants is desensitized to the allergens—that means that they can eat the foods that in the past were considered life threatening. More recently, we have been pursuing treatment courses in immunotolerance that are aimed at making immunotherapy accessible to more children.
Studying Root Causes
However, while the expansion of immunotherapy to food allergens is an almost miraculous prospect, we also need to look at how this maladaptation comes about. If immune disorders such as allergies are responses to changes in the way our bodies interact with the environment in the gut, the lungs, sinuses, and skin, it is critical that we understand the mechanisms involved. It makes greater public health and financial sense to treat the root causes in addition to treating the disease. While OIT may look like magic to families that already have food-allergic children, it still requires years of commitment and money.
That is why I would like to discuss another area of research* I have been involved with in which we have already uncovered a cause-and-effect relationship between an environmental trigger–ambient air pollution (AAP)–and an allergic disease—asthma. Asthma is the most frequent chronic disease in children.
You may be familiar with the term epigenetics. This involves not the characteristics encoded in the DNA but rather the “expression” of those genes, i.e. when and how they reproduce themselves in different cells throughout the body. A process called DNA methylation decreases expression and function of genes, most pertinently for our purposes, a gene called Foxp3, which is key to the work of so-called Regulatory T (Treg) cells. These “peace-keeping” cells prevent excessive immune responses. Children lacking Foxp3 have greater incidence of severe allergies, asthma, gastrointestinal disease and type-1 diabetes than those with normal Foxp3. Because AAP exposure can induce epigenetic changes we hypothesized that Treg-cell function would be impaired by high levels of air pollution, amplifying the inflammatory response.
Children with and without asthma from Fresno, California, which has high levels of black carbon air pollutants, were compared with those from Stanford, California, which has much cleaner air. We used peripheral blood Treg cells in functional and epigenetic studies. Asthma severity was assessed by a score derived from criteria in the Global Initiative for Asthma. Foxp3 was measured in respect to genetic expression, Treg-cells function and asthma-symptom score.
We found that increased exposure to AAP is associated with hypermethylation—suppression–of Foxp3. The gene was there but, as predicted, it wasn’t working fully because of the chemical assault by pollutants. In all 3 measurements, Foxp3 expression was lowest for the Fresno-asthmatic group, next lowest for Fresno non-asthmatics, higher for Stanford subjects with asthma, and highest for the Stanford group without.
In other words, air pollution alters genetic function so that the immune systems of non-asthmatic children begin to mimic those of asthmatic children, and already-asthmatic children get worse. If, as has already been proven in other research, these epigenetic changes can be inherited by the next generation, it would account for the increasing severity of allergic disease from one generation to the next that we have seen in the past few decades. We have found that if one parent has an allergy of any kind, their child may have a 65% chance of developing an allergy. If both parents have allergies, the likelihood can climb to as high as 85%.
The science is moving as fast as our funding will allow. This relationship between a form of pollution and an impaired immune system leads us to think that other environmental links can be found. We may well find that food additives, antibiotics, climate change, and the rest of the usual suspects are indeed contributing to the epidemic. Actually doing something about it will require an extraordinary cooperative effort. Finding cures for both effects and causes is becoming increasingly urgent.
Dr. Nadeau is Associate Professor, Stanford Medical School and Lucile Packard Children’s Hospital Division of Immunology and Allergy. Director of Basic Science and Clinical Research of SAFAR (Stanford Alliance of Food Allergy Research). Chief Investigator for all food allergy studies at Stanford.
*Ambient air pollution impairs regulatory T-cell function in asthma
Journal of Allergy and Clinical Immunology. 2010 Oct;126(4):845-852.e10. Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J, Tager I.
Thank you Dr. Nadeau.
My son consumes 8 peanuts a day in the maintenance phase of desensitization. Sometimes when I tell others that OIT is “safe and effective,” they say they are glad it’s working for my son but their child has multiple food allergies.
It’s inspiring to learn of your 100% success rate desensitizing those with multiple food allergies.
And had we known 8 years ago, living across the viaduct from P&G might contribute to my son developing a life-threatening food allergy, we would have simply moved.
Keep up the life-saving work and may money rain down upon you!
Thank you for a wonderful and informative article. Are eyes subject to immune disorders as well as skin, gut, etc?
Thanks for writing. If by “immune disorders” you mean allergies, yes indeed. This, in part, is what WebMd has to say about eye allergies: “Like all allergies, eye allergies are caused by a glitch in the body’s immune system. The trouble starts when the conjunctiva (the mucous membrane that lines the eyelids and covers the whites of the eyes) comes into contact with something that, while actually harmless, is seen as a threat. In a mistaken attempt to fight off the threat, the immune system makes antibodies that cause your eyes to release histamine and other substances. That, in turn, makes eyes red, itchy, and watery. Eye allergy symptoms can happen alone or along with nasal allergy symptoms.” For more, go to http://www.webmd.com/allergies/eye-allergies