Oral immunotherapy
Oral immunotherapy (OIT) is a method of treatment for reducing negative or adverse reaction to allergens by oral administration of limited amounts of the allergen. OIT is currently under investigation as a treatment for a variety of common food allergies including peanuts, milk, and eggs. Studies involving OIT have shown desensitization towards the allergen.[1] However, there are still questions about longevity of tolerance after the study has ended.[2][3]
Course of treatment begins in a hospital or clinic, but can eventually be done at home. Many studies at first worked to reduce reaction due to accidental allergen exposure, but more studies are moving to get rid of adverse reaction completely. Though most patients experience mild symptoms on the first day, severe reaction is rare, occurring in <2% of subjects in each study.[1] However, almost every study has excluded patients with severe allergen-induced anaphylaxis.[4]
Mechanism of action
In recent years, a large amount of data have been collected about the function of oral immunotherapy in immune function. Data show the involvement of allergen-specific regulatory T-cells (Tregs), which help limit immune response, as well as the deletion of effector T cells (TH2 cells) which stimulate antibody production, involving the decrease of two signaling molecules, IL-4 and IFN-y.[5] OIT Also creates an increase in allergen-specific IgG4 antibodies and a decrease is allergen-specific IgE antibodies, as well as diminished mast cells and basophils, two cell types which are large contributors to allergic reaction.[3][4]
Protocol
OIT involves taking a dose of the allergen daily mixed in with food. Over time, this dose is increased to develop higher levels of immunity. For oral immunotherapy, current protocols have 3 phases:
- 1) On the first day of treatment, patients are given increasing doses of the allergen at short time intervals while being watched by a doctor. This is called an initial dose escalation or rush desensitization. Vitals are measured along with a physical exam. If the patient shows any symptoms, dosing for that day is finished. The largest tolerated dose given is the prescribed dose for the patient, taken twice a day.
- 2) In the next 6–12 months, an increased dose is given under supervision, where the patient is monitored. If the patient doesn't have a reaction, the new dose will be prescribed. This is called the build up phase.
- 3) In the final phase, which can be months or years, there is the maintenance phase with daily home dosing.[1]
Reactivity is tested using oral food challenges or with skin prick tests. Phases 1&2 are conducted in a supervised clinical setting. However, phase 3 can be done at home.[3]
Current research
A variety of new approaches are currently being tested to improve efficacy of oral immunotherapy.
One approach being studied is in altering the protein structure of the allergen to decrease immune response while still developing tolerance for the patient. Extensive heating of some foods can change the conformation of epitopes recognized by IgE antibodies. In fact, studies show that regular consumption of heated food allergens can speed up allergy resolution. In one study, subjects allergic to milk were 16x more likely to develop complete milk tolerance compared to complete milk avoidance. Another approach regarding changes in protein is to change specific amino acids in the protein to decrease recognition of the allergen by allergen-specific antibodies.[4]
Another approach to improving oral immunotherapy is to change the immune environment to prevent TH2 cells from responding to the allergens during treatment. For example, drugs that inhibit IgE-mediated signaling pathways can be used in addition to OIT to reduce immune response. In 1 trial, the monoclonal antibody omalizumab was combined with high-dose milk oral immunotherapy and saw positive results. Several other trials are also currently being done combining omalizumab with OIT for a variety of food allergens. FAHF-2, a chinese herbal mixture, has shown positive effects on the immune system and has been shown to protect mice from peanut-induced anaphylaxis. FAHF-2 was also well tolerated in a phase I study. While it is possible that omalizumab, FAHF-2 or other immunomodulatory agents alone might be able to treat dangerous allergies, combining these with OIT may be more effective and synergistic, warranting further investigation.[4]
In addition, nanoparticles is a field of development that can be used for OIT. With the potential to modulate antigen release, it may one day be possible to take a pill containing nanoparticles that will modulate dosing, requiring fewer office visits.[4]
Studies have also been done to determine the efficacy of OIT for multiple allergens simultaneously. One study concluded that multi-OIT would be possible and relatively, though larger studies would be necessary.[6]
Currently, though studies are being performed by scientists and doctors around the world, there is not yet an over-the-count oral immunotherapy treatment or standardized treatment plan for doctors.[1]
See also
References
- ↑ 1.0 1.1 1.2 1.3 What is Oral Immunotherapy? - OIT Center
- ↑ Land MH, Kim EH, Burks AW (May 2011). "Oral Desensitization for Food Hypersensitivity". Immunol Allergy Clin North Am 31 (2): 367–376. doi:10.1016/j.iac.2011.02.008. PMC 3111958. PMID 21530825.
- ↑ 3.0 3.1 3.2 Uyenphuong HL, Burks AW (2014). "Oral and sublingual immunotherapy for food allergy". World Allergy Organization Journal 7 (1): 35. doi:10.1186/1939-4551-7-35.
- ↑ 4.0 4.1 4.2 4.3 4.4 Moran TP, Vickery BP, Burks AW (2013). "Oral and sublingual immunotherapy for food allergy: current progress and future directions". Current Opinion in Immunology 25 (6): 781–787. doi:10.1016/j.coi.2013.07.011. PMC 3935613. PMID 23972904.
- ↑ Wisniewski JA et al. (March 2015). "Analysis of Cytokine Production by Peanut-Reactive T Cells Identifies Residual Th2 Effectors in Highly Allergic Children Who Received Peanut Oral Immunotherapy". Clin Exp Allergy. doi:10.1111/cea.12537. PMID 25823600.
- ↑ Begin P et al. (Jan 2014). "Safety and feasibility of oral immunotherapy to multiple allergens for food allergy". Allergy Asthma Clin Immunol 10 (1): 1. doi:10.1186/1710-1492-10-1. PMC 3913318. PMID 24428859.