What is the mechanism of action of allergen-specific immunotherapy (ASIT)?

From the Guidelines

Allergen-specific immunotherapy works by gradually exposing the immune system to increasing amounts of an allergen, helping it develop tolerance over time, as supported by the most recent study in 2024 1. The treatment involves regular administration of allergen extracts through injections (subcutaneous immunotherapy) or under-the-tongue drops or tablets (sublingual immunotherapy) for 3-5 years.

• For subcutaneous immunotherapy, patients typically receive weekly injections during a build-up phase (3-6 months), followed by monthly maintenance injections.
• Sublingual immunotherapy involves daily self-administration at home after the first dose is given under medical supervision. Common allergens treated include pollens, dust mites, animal dander, and insect venoms. The therapy modifies the immune response by shifting from an allergic Th2 response to a more tolerant Th1 response, increasing regulatory T cells, and producing blocking antibodies (IgG4) that compete with IgE antibodies, as described in a clinical practice guideline in 2024 1. This leads to reduced mast cell and basophil activation, decreased inflammatory mediator release, and ultimately diminished allergic symptoms. Patients should be aware that improvement typically occurs gradually over months to years, and treatment requires commitment to the full regimen for lasting benefits, with a minimum duration of 3 years recommended to achieve disease modification and long-term clinical and immunological tolerance, as suggested by a study in 2024 1. It is also important to note that the decision to continue or stop immunotherapy should be individualized, taking into account the severity of disease, benefits sustained from treatment, and convenience of treatment, as stated in a study in 2024 1. Additionally, a study in 2008 1 highlights the importance of considering the patient's history, exposure, and diagnostic test results when selecting allergens for immunotherapy, and that allergen immunotherapy may prevent the development of new allergen sensitizations and reduce the risk for the future development of asthma in patients with allergic rhinitis. However, the most recent and highest quality study in 2024 1 provides the most up-to-date guidance on the optimal duration of allergen immunotherapy.

From the Research

Mechanism of Allergen Specific Immunotherapy

• Allergen specific immunotherapy is the administration of increasing amounts of specific allergens to which the patient has type I immediate hypersensitivity 2, 3.
• It is a disease modifying therapy, indicated for the treatment of allergic rhinitis, allergic asthma, and hymenoptera hypersensitivity 2, 3.
• The main mechanism of allergen specific immunotherapy is to induce allergen tolerance through modification of innate and adaptive immunologic responses 4.
• Humoral, cellular, and tissue level changes occur with allergen immunotherapy, including:
  • Large increases in antiallergen IgG(4) antibodies 2, 3.
  • A decrease in the postseasonal rise of antiallergen IgE antibodies 2.
  • Reduced numbers of nasal mucosal mast cells and eosinophils 2.
  • Induction of Treg cells 2, 3, 4.
  • Suppression of Th2 more than Th1 lymphocytes 2, 3.
  • Induction of allergen-specific regulatory T and B cells, interleukin 10, and transforming growth factor β production 3, 4.

Administration and Indications

• Allergen immunotherapy can be administered either subcutaneously in the physician's office or sublingually by the patient at home 2, 3.
• Indications for allergen immunotherapy include:
  • Inadequate symptom control despite pharmacotherapy and avoidance measures 2, 3.
  • A desire to reduce the morbidity from allergic rhinitis and/or asthma, or reduce the risk of anaphylaxis from a future insect sting 2, 3.
  • When the patient experiences undesirable adverse effects from pharmacotherapy 2, 3.
  • When avoidance is not possible 2, 3.

Benefits and Future Directions

• Allergen specific immunotherapy can prevent the development of new allergic sensitizations and/or new-onset asthma 2, 3, 5.
• The use of immunotherapy in food allergy is still under investigation 3, 5.
• Combination of allergen immunotherapy with other treatments, such as omalizumab, may be useful in reducing adverse events and allowing its use in patients with more severe or uncontrolled asthma 6.
• Novel routes of administration, such as intra-lymphatically and epicutaneously, are being developed 4.