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