Allergen immunotherapy

Question 1

What is allergen immunotherapy?

Answer 1

Treatment for IgE mediated (type 1) allergies such as hay fever, venom allergy, allergic asthma, and immediate-type food allergy.

Question 2

What are the immunological hallmarks of type I allergy?

Answer 2

• Allergen-specific IgE antibodies
• Allergen-specific Th2 cells
• ILC2 (Innate Lymphoid Cells type 2) cells
• IL-4, IL-5, IL-13
• Effector cells of allergic response (Mast cells/basophils and Eosinophils)

Question 3

What is allergen immunotherapy treatment?

Answer 3

• Exposing the allergic patient to the allergen source they are allergic to, starting at a very low dose and slowly increasing it to a high maintenance dose
• Originally, all AIT was administered via monthly subcutaneous injections (SCIT), but later also via daily sublingual drops or tablets (SLIT).
• For good efficacy, at least 3 years of treatment are needed. After that in the majority of patients, tolerance remains intact, even if AIT is discontinued (big advantage compared to symptomatic treatment).

Question 4

What is the mechanism of AIT?

Answer 4

To inhibit the immune response to allergens at several points in the reaction.

Question 5

What parts of the immune response to allergens can blocking antibodies modulate?

Answer 5

• Block IgG antibodies
• Block allergens from reaching mast cells and basophils: block induction of the release of mediators
• Block allergen reaching memory B-cells: block further expansion of IgE producing plasma cells
• Block facilitated antigen presentation through CD23 (the B-cells that were acting as antigen-presenting cells to enhance the Th2 response)

Question 6

Why is allergen immunotherapy used so little if it has the potential to get so close to a cure?

Answer 6

AIT means exposure to a high-dose of allergen which can induce potentially severe side-effects.
• AIT needs to be given for at least 3 years, which is a burden for the patient, requiring monthly visits to the doctor and AIT really requires treatment discipline to work.

Question 7

What are the challenges for allergen immunotherapy?

Answer 7

• Long-lived IgE plasma cells hide in bone-marrow and target organs. They provide a very persistent supply of allergen-specific IgE. It takes years of AIT before IgE titers come down.
• Natural exposure to the allergen is extremely low. Exposure to e.g. grass pollen allergen during a whole season is in the ng range! Even if a very efficient induction of a good immune memory for a protective Treg/Breg/IgG4 is achieved, the question remains whether natural exposure is high enough to trigger it.