Allergy immunotherapy or immune therapy (AIT) is used to treat many allergic conditions. About 50 million people experience allergies every year in the US alone, of which about 3 million are treated with allergy shots.

What is AIT?

AIT is based on the principle of introducing allergens in small doses over a long period, to induce desensitization. Some conditions in which AIT is useful include allergic asthma, allergic rhinitis, allergic conjunctivitis and allergy to stinging insects.

The concept was first introduced in 1911 by Noon, an English physician, who gave patients with hay fever injections of timothy grass extract. This treatment was followed by remarkable increases in tolerance to the allergen at 100 times the original dose. This has evolved to modern immunotherapy via the use of standardized allergens and immunotherapy, as described by Robert Cooke in 1916.

The benefit of AIT is its long-lasting effect, which keeps the previously sensitized individual free of allergic symptoms over the long term. This is therefore a more cost-effective approach for many allergy sufferers than medical treatment.

Allergy shots are suitable for patients of all ages, though not usually given to children below 5 years who may not be able to communicate side effects they experience and are generally unwilling to receive repeated injections.

The greatest benefit is likely in those patients who experience prolonged periods of allergic symptoms each year, and those who have severe symptoms including anaphylactic reaction. Those who feel that their symptoms are not helped much by medical treatment and avoiding environmental triggers, and those who dislike being on medications for a long time may also be good candidates for AIT.

Asthma immunotherapy in clinic. Image Credit: Artur_eM / Shutterstock

Mechanism of action of AIT

Allergies occur when the body recognizes a substance as being foreign and activates the immune response. This causes antibody release and binding to the allergen. The binding also causes the release of several bioactive substances like histamine from many immune cells. The majority of allergic symptoms is due to histamine release.

The strange thing about an allergic reaction is its selectivity, in that the same substance which causes no reaction in the majority of people provokes a significant immune activation in the allergic individual.

AIT is designed to work somewhat as a personalized vaccine devised from the allergenic substance. The minute doses stimulate the immune system very slightly, building up a different type of immunity which is less troublesome than the first, and enabling the allergic individual to tolerate normal levels of the offending allergen.

Following the initiation of AIT, the early response is shown by mast cells and basophils, which stop releasing histamine and other irritant chemicals. The intermediate response is marked by a shift in relative numbers of various T cell types, with more Treg cells which modulate the allergic response, and fewer Th2 cells. Trf cells become active and release various cytokines like IL-10 and TGF-β, that finally cause immunological tolerance to the allergen.

The late changes include reduced IgE antibody production by B cells with increased IgG4 and IgA antibodies. This is marked by clinical improvement, mediated by IL-10, which also suppresses the inflammation caused by the degranulation of mast cells, basophils and eosinophils.

AIT takes much longer than anti-allergic drugs like cetirizine to control allergy symptoms. The period may sometimes be up to one year, with maintenance treatment continuing for another 3-5 years. The effectiveness may be related to the dosage and duration of AIT.

A more recent innovation is sublingual immunotherapy (SLIT) in which the allergen is placed under the tongue in the form of drops or tablets. This therapy is far less likely to cause any adverse reactions, so it is safe to be self-administered at home. However, each tablet or drop works against only one allergen. At present, SLIT is available for treating ragweed, grass pollen and dust mite allergies.

Does AIT actually work?

Benefits of AIT include:

• Reduced allergic symptoms
• Reduced chances of new allergies
• Reduced risk of asthma in children with allergic rhinitis

Failure of AIT may be due to:

• Unduly low doses of allergens
• Failure to sensitize against one or more potent allergens
• High environmental exposure to the allergen
• Increased exposure to irritants like tobacco smoke

Does AIT cause side effects?

These shots can cause severe adverse reactions like anaphylaxis. An anaphylactic reaction is the highest grade of hypersensitivity response which can even kill the person. The symptoms include nausea, swelling of the throat, tightness of the chest, and wheezing, with dizziness.

For this reason, AIT is given only in the doctor’s office where this can be immediately identified and treated. Patients are usually asked to wait for half an hour after the shot before going home to rule out such an occurrence. Milder reactions include redness at the site with swelling, while some patients have sneezing, nasal congestion or urticarial rashes consisting of raised red patches on the skin. Alum-absorbed extracts seem to be somewhat safer than aqueous extracts because of their slower absorption.

Oral immunotherapy, using tiny doses of the allergenic food by mouth, is also being given experimentally to treat food allergies. For example, preliminary studies of young children with peanut allergy show that it may be possible to decrease their sensitization under carefully controlled exposure to peanuts.

How is AIT carried out?

Treatment occurs in two phases:

• The build-up phase where the dose of allergenic substance is increased with shots being given 1-2 times a week. The total duration ranges from 3-6 months but may vary with the number of shots given.
• The maintenance phase in which the patient has received the effective dose that stimulates the immune system, depending on the prior exposure, level of sensitization and response in the build-up phase. The intervals between shots will be longer.

The steps are:

• Identification of the allergen
• Weekly small doses graduated to reach the effective dose
• Continuing this dose weekly or fortnightly for up to a year
• Reassessing for efficacy, and either stopping if ineffective, or switching to maintenance phase if found useful. This consists of monthly shots for the next 3-5 years

This is the conventional protocol. The cluster protocol uses several injections on the same day, with a week’s interval before the next cluster. The rush protocol compresses the whole set of graduated-dose challenges into a single day. The safety is greatest with conventional immunotherapy, but the rush protocol allows for full protection in a few days. Rapid desensitization may be used in urgent medical situations in which a patient would gain substantial immediate benefit by being able to safely receive a life-saving medication to which the patient was formerly sensitized to.

Nowadays recombinant allergens are being used to improve the efficacy at lower risk.

Sources

• Luong, A. (2009). Understanding the Mechanism of AIT. med.uth.edu/…/
• Harvard.edu. (2018). Allergy Shots (AIT). www.health.harvard.edu/…/allergy-shots-allergen-immunotherapy-a-to-z
• Wu A. Y. (2012). Immunotherapy – Vaccines for allergic diseases. Journal of Thoracic Disease. https://dx.doi.org/10.3978%2Fj.issn.2072-1439.2011.07.03
• Chen K-W., et al., (20187). Ragweed Pollen Allergy: Burden, Characteristics, and Management of an Imported Allergen Source in Europe. International Archives of Allergy and Immunology. https://doi.org/10.1159/000487997