AIT regulations, biological potency, and link to clinical effect.
The characterization of the main allergenic molecules led to the development of quantification methods and their progressive incorporation into regulations of extract preparation of AIT. In parallel, Create International project ended in the first available reference methods for major allergen content determination3,24-26. Today, for any AIT product intended for human use, a proper measurement of biological potency and major allergen content is required. Major allergens use to be the most abundant proteins of allergenic sources and their content in AIT products is closely related to total biological potency. Moreover, most of the patients included in clinical trials are sensitized to major allergens and in a significant percentage monosensitized to them27. In consequence, as a general criterium, patients elected for AIT must be sensitized to major allergens as there is no evidence of the clinical effect of AIT products in patients sensitized only to minor allergens. Unfortunately, the content for minor allergens in AIT preparations is, in the vast majority of cases, unknown and variable. In areas where pollen exposure is very intense, and sensitization to minor allergens is very frequent, side reactions to AIT preparations containing assigned to minor allergens variability have been described28,29.
Main AIT mechanisms involve early effector cells de-sensitization and progressive onset of tolerance through a regulatory response that needs at least three years to be consolidated5,13. Dose-finding studies are usually performed during relatively short times, and thus effective dose is adjusted to target desensitization mechanism and to major allergen doses