General Medical Information

Immunotherapy

Richard L. Mabry

The only measure that offers a possible cure for allergy is immunotherapy. It should not be considered a last resort, and the advantages may be evident at any point in the course of management. Most candidates for allergen immunotherapy meet the following criteria:

They have symptoms not easily controlled with pharmacotherapy.
They are sensitive to allergens that cannot be readily avoided.
They have symptoms that span two or more allergy seasons or are severe. They are willing to cooperate in a program of immunotherapy.

Immunotherapy involves parenteral administration of antigens identified with appropriate in vivo or in vitro tests to (theoretically) stimulate formation of allergen-specific IgG-blocking antibodies, which eventually compete with IgE antibodies for target sites on mast cells or basophils.

Throughout an average ragweed season, a typical patient is exposed to a total of less than 1 mg of ragweed antigen E. Immunotherapy with ragweed, on the other hand, approaches levels of 40 to 1,000 mg of antigen per injection. Among experimental animals, chronic exposure to small antigen doses increased IgE production, whereas large doses of antigen administered parenterally have been shown to suppress IgE formation and produce IgG (blocking antibodies). From this, we see that (a) small initial doses of immunotherapy can and typically do cause an initial increase in IgE, (b) continued therapy at appropriate doses causes IgE production to decrease and IgG (blocking antibody) production to increase, (c) parenteral therapy is necessary to deliver high enough doses to stimulate formation of blocking antibody, and (d) long-term therapy with very low antigen doses can worsen rather than improve the patient’s condition.

In addition to an initial increase followed by a gradual decline in specific IgE levels coupled with a gradual (dose-dependent) increase in IgG-blocking antibody levels, immunotherapy produces cellular changes that include decreased reactivity of basophils and lymphocytes. There are no conclusive data on the exact mechanism of immunotherapy, although it is postulated that it involves changes in TH1 and TH2 ratios as well as effects on cytokines.

Immunotherapy based on skin end-point titration or in vitro methods usually is administered once or twice a week until symptomatic response occurs. Treatment is continued weekly for at least 1 year, every other week for another year, and every 2 to 3 weeks for a third year. These are guidelines, and the physician must adjust dosage and duration of therapy for each patient. If immunotherapy does not produce the expected benefit, the physician must consider such factors as increased antigen exposure, an imbalance in the treatment mix, or other antigens for which testing and possible treatment are needed; inappropriate immunotherapy doses; other triggers such as foods, chemicals, irritants, or infection; or an incorrect diagnosis of atopy. Immunotherapy should be prescribed and administered under the supervision of an appropriately trained physician who is prepared to manage anaphylaxis.