Allergen Immunotherapy (Desensitization)

Allergen Immunotherapy (Desensitization)

Desensitization or hyposensitization is increasingly being prescribed therapeutically with an aim to reduce environmental allergen-specific IgE-mediated sensitivity in hypersensitive (atopic) individuals and to reduce demands on constrained health services (Dwyer, 1993). Low doses of offending allergens are slowly introduced to the immune system via subcutaneous or sublingual modes of delivery.

Patients who tolerate the allergen exposure have these doses progressively increased, initially by volume and subsequently by concentration of the specific mixtures referred to as the “build-up” phase. Doses are delivered weekly in the case of injections or daily with oral drops under the tongue. These regimes are becoming more standardized and generally agreed upon by national and international allergy and immunology societies.

How does it work?

IgE sensitizes mast cells and basophils by binding to the receptor for the antibody on their surfaces. When exposed to the natural allergen, the mast cells and basophils release histamines, prostaglandins, cytokines and chemokines producing the immediate type I allergic reaction seen in patients with allergic rhinitis, for example. After the initial allergic phase, further inflammation occurs leading to other clinical symptoms such as allergic rhinoconjunctivitis, eczema, asthma and systemic anaphylaxis.

Allergen-specific immunotherapy is the only treatment that leads to prolonged tolerance against allergens  (Lockey & Ledford, 2014).

One such evolved theory for allergen immunotherapy is that at around 6-8 weeks after commencing treatment, interleukin-10 (IL-10) is produced and promotes production of allergen specific IgG4 from B cells and reduces proinflammatory cytokine release from mast cells and turns down eosinophil activity. When natural exposure to the allergen occurs the already present IgG antibodies compete with or block the IgE effector mechanisms including basophil histamine release therefore preventing the excessive chemical reactions that cause allergy symptoms.

Biopsies taken from the skin and nasal mucosa of patients on allergen immunotherapy reveal reductions in inflammatory cell numbers including mast cells, basophils and eosinophils.

Most researchers don’t disagree entirely with this theory, however more recent studies have found T cells that regulate IgE production to specific allergens may be stimulated by the low doses of the allergens during immunotherapy, generating immune tolerance to the allergen.

Another possible reason for allergen immunotherapy’s role in producing immune tolerance may be due to the induction of allergen-specific IgA, which has been observed; these antibodies can induce monocytic cells to produce IL-10, the immunoregulatory cytokine discussed above.

Allergen specific Treg cells (regulatory T cells) and their subsequent suppression of cytokine production are important in producing tolerance to environmental allergens. Studies of allergen immunotherapy via the sublingual route indicate peripheral T cell tolerance due to Treg cell induction in the sublingual mucosa following treatment (Lockey & Ledford, 2014).

What does the future hold?

While researchers continue to seek the exact scientific mechanisms to explain how allergen immunotherapy induces tolerance, suffering patients who are sensitive to environmental allergens such as grasses, weeds, trees, cat dander particles and dust mites have shown impressive results to this form of treatment. Oftentimes, these individuals experience a reversing of their symptoms of the skin, lungs, nose and eyes — especially in patients with allergic rhinitis and/or allergic conjunctivitis conditions. Long term allergen specific tolerance has been clinically observed following allergen immunotherapy.

References

Dwyer, John M. The Body at War: How our immune system works. 2nd ed. 1993.

Lockey, Richard F and Ledford, Dennis K. Allergens and Allergen Immunotherapy: Subcutaneous, sublingual and oral. 5th ed, CRC Press, Taylor & Francis Group, LLC. 2014.