Tolerance in a Test Tube: Novel Study Points Way Towards Relief from Severe Food Allergies

By Dr. Xiu-Min Li, Dr. Paul Ehrlich, and Dr. Purvi Parikh

Because there has never been an approved treatment for food allergies, there has never been an incentive to measure patient progress during therapy. Instead, patients have managed the problem by avoiding the foods and preparing for emergencies while waiting for nature to take its course; either a patient will outgrow an allergy or not. Allergen-specific IgE levels in the blood may rise and fall without predicting the likelihood of a serious allergic reaction at a given moment. Food challenges are the truest test, but they are not suitable for periodic use, and are so anxiety provoking that many people don’t try them even after their allergist recommends it. If, however, a reasonably expeditious long-term treatment could be found, tools to show “tolerance in a test tube” would be warranted.

That moment is at hand, and is the premise of a new study we are planning to undertake called, “Practice-Based Bio-Marker Study Using Traditional Chinese Medicine to Assess Real Life Effects on Patients with Poly-Allergen Sensitization.” The past several years, have seen great progress in treating food allergies with compounds taken from traditional Chinese medicine (TCM), specifically a botanical drug called FAHF-2 (food allergy herbal formula) and now a refined, much-more-potent version called B-FAHF-2.* The results to date are sufficiently encouraging to treat patients in a practice-based study and to see if we can measure progress by examining changes in the blood chemistry. Ten patients, from ages 2 to 16, will receive Chinese herbal formulas as a medicinal foundation with adjunct therapies such as acupuncture and acupressure. The plan is to use the new biomarkers along the way with the goal of better predicting successful food challenges for patients as treatment progresses. This study is small. It can best be described as a “proof of concept.” The results, if encouraging, may be useful as the basis for a larger study later on. Eventually, it could be employed for other, non-TCM experimental therapies.

We plan to look at several bio-markers—chemical indicators that correspond to changes in immune activity. One is basophil activation. Basophils and mast cells are effector cells. They both contain mediators, such as histamines, that are released when they encounter an allergen. Unlike mast cells, which are lodged in tissue, basophils circulate in the blood and are easily extractable with a minimal blood draw. Exposed to antigens in a laboratory, basophils can be activated, producing, in effect, an allergic response at no risk to the patient. Basophil activation tests (BATs) are used in research, but if treatment becomes more widespread, they may become more common at the practice level.

Another is DNA methylation by the Th1 and Th2 cells. DNA methylation determines “gene expression”—turning on and off cellular secretion of certain cytokines (small proteins that help regulate the immune response). In a healthy immune system, Th1 cells dominate, helping fight infectious disease. In an allergic individual, Th2 cells, which are normally associated with fighting invasive parasites, are too powerful, and they attack proteins in things like pollens and foods. We plan to study two markers: 1) IFN-gamma, the principal Th1 effector cytokine, which plays a crucial role in counteracting and suppressing Th2 responses of allergic diseases. It is deficient in food allergic patients. 2) RANTES (CCL5), which is highly secreted in food allergy patients and plays an important role in recruiting basophils, eosinophils, and T cells into the inflammatory sites.

The protocol

Although oral food challenge is the gold standard for diagnosis of food allergy, patients with a history of severe reactions and high levels of IgE are understandably reluctant to undergo food challenge at baseline. Thus, there will be no initial challenge as there is in some research.

This is a practice-based study. There will be no placebo controls (everyone will receive TCM treatment). However, there will be an observational control group supplied by an in vitro blood sampling of patients with poly-allergen sensitization who have never received TCM or other treatments beyond that of a medically restricted diet. These untreated samples will undergo the same tests of the treated blood for comparison.

If patients’ immunological responses (IgE levels and basophil activation and T cell epigenetic status) are dramatically improved by treatment compared to baseline, and if the family is interested in introducing certain foods, we plan to determine clinical tolerability using standard allergy protocols, or perhaps using newer tools now in development that are considered highly predictive of the results of a food challenge. The goal is, of course, the ability to eat a broader range of nutritious food without fear of a reaction.

Unlike other studies, in which subjects usually have a narrow set of allergic conditions at baseline, this one is more like the “real world” of food allergic patients. Those with severe food allergies often have other allergic diseases, and they can take part in this research, where in other studies they might be excluded. This study should also be suitable for children with multiple food allergies who have histories of severe reactions. It is patient friendly and cost effective. The data will be helpful for designing a controlled, perspective study and for NIH funding applications in the future. If successful, this protocol can be adopted by other allergists in their practices. Also, because TCM is inherently an individualized approach to medicine, other herbal drugs, as well as acupuncture and acupressure, may be used for different patients depending on their other conditions. This will not compromise the integrity of the bio-marker data.

Who Will Be Eligible?

To participate, patients must be 2-16 years old with a convincing history of anaphylaxis to peanut and tree nut, plus one of the following categories:

1. Peanut and/or any tree nut, or seeds specific IgE levels >100 KU/L.
2. IgE levels >15 KU/L that increased over the last two years
3. Frequent and potentially severe reactions (>1 reaction per month)
4. Baseline basophil activation > 60% in response to allergen (peanut and/or tree nut) stimulation

Other aspects to be considered

• Normal lab data on CBC and Comprehensive metabolic panel; however, distinct from studies of oral immunotherapy for food allergies (OIT) and other experimental treatments, patients with an elevated percent of blood eosinophils will not be excluded. Patients with elevated peripheral percentages of blood eosinophils, and significant co-morbidities such as environmental allergies or eczema are typical of Poly-Allergen Sensitization, and cannot be omitted from a real world study.
• OIT drop out patients, previous TCM, or other alternative-therapy-treated patients are welcome to participate in this study. A percentage of this population has shown reduction of poly-sensitization symptoms. Because they are poly-sensitized with multiple food allergens, some have successfully passed challenges on some of the foods, but not all. Their best hope is to continue on TCM and introduce more foods. By testing for the degree of basophil sensitization and T cell epigenetic changes, we can use their current IgE levels, basophil sensitization, and T cell epigenetic profile and document those changes to provide a baseline for established patients. The improvement of these bio-markers may be a good indication that future TCM patients will be able to tolerate that particular food.
• Patients with primary eosinophilic esophagitis (i.e. EoE without IgE-mediated food allergies) will not included in this study since primary EoE patients do not have highly elevated IgE levels and abnormal basophil activation is not a major concern.

 

• All participants must agree to follow the current TCM protocol.

TCM therapy

Patients will receive TCM therapy at an off-site TCM clinic (Ming Qi Natural Health Care Center) from Dr. Li. TCM treatments will include pills, teas, baths, and creams. Acupuncture/acupressure treatment will also be included at TCM visits. Allergy services will be provided at Allergy & Asthma Associates of Murray Hill, which will also monitor all bio-marker data.

We plan to use B-FAHF-2 as a baseline remedy, as well as acupuncture or acupressure, though frequency may vary. An established protocol will also allow for the use the other herbal remedies, depending on the real life conditions.  Specifically: There will be remedy A (B-FAHF-2); Remedy B (herbal cream); Remedy C (digestions tea); Remedy D (IgE tea).

Next Steps

This study will be funded by private donations. Once the seed funds have been received several months of paperwork must be completed, followed by active recruitment of patients according to the criteria listed above. Treatment for those accepted can begin at once. Unlike NIH-sponsored trials, patients will be responsible for certain costs. However, these will be limited because the appropriate allergy services will be offset by insurance, and the tests, which are generally only used for research, will be conducted by Dr. Li’s laboratory colleagues instead of being charged to outside providers. Logistically, the process is complicated by the fact that the blood samples will have to be processed within tight time frames, but because the testing personnel are already in place, new staff will not be required.

We think this represents a very significant step towards the eventual widespread practice of food allergy treatment in which considerable suffering may be relieved while children are still children.

{Note: This study is now beginning the fundraising stage. It is not recruiting patients yet. If you wish to contribute and/or learn more about the research as news becomes available, please join the Facebook group, Chinese Herbs for Allergies. To read more about this study, and make a donation if you wish, click here.)

*(The story of this research is told in Henry Ehrlich’s book, Food Allergies: Traditional Chinese Medicine, Western Science, and the Search for a Cure.)

Dr. Xiu-Min Li is Professor of Pediatrics in the Division of Pediatric Allergy and Immunology at the Icahn School of Medicine at Mount Sinai in New York. She has published her research in The Journal of Allergy and Clinical Immunology and other top journals. She did her medical training at Stanford and Johns Hopkins, as well as Henen Medical University in China.

Dr. Paul M. Ehrlich practices at Allergy and Asthma Associates of Murray Hill, and is clinical assistant professor of pediatrics at New York University School of Medicine. He is a fellow of the American Academy of Pediatrics, the American Academy of Allergy, Asthma & Immunology, and the American College of Allergy, Asthma & Immunology. He has been featured as one New York’s top pediatric allergists in New York Magazine for many years. He is co-author of Asthma Allergies Children: a parent’s guide and a founder/blogger at this website.

Dr. Purvi Parikh is an adult and pediatric allergist and immunologist. She completed her fellowship training in allergy and immunology at Albert Einstein College of Medicine’s Montefiore medical center following her residency at the Cleveland Clinic and is board certified by the American Board Allergy and Immunology, as well as the American Board of Internal Medicine. She works with Dr. Ehrlich at Allergy & Asthma Associates of Murray Hill.