KEYWORDS
Allergy, affinity, antibody, IgE, IgG.1 Introduction
The discovery of IgE-mediated allergic disease as an indication of
hay-fever, or allergic rhinitis, was first described in 1819 by John
Bostock, a medical doctor who himself suffered from hay fever1. He called the disease catarrhus aestivus, summer
catarrh, as it was invariably absent in winter time. Catarrhus aestivus
was a rare disease in the early nineteenth century, and after reporting
his own case, it took him more than nine years to identify another 28
cases for publishing a second article 2. At the
beginning of the 20th century, allergens were
considered being toxins 3. Only with the discovery of
IgE antibodies 4,5, it became evident that
allergen-specific antibodies are the reason for the aberrant response of
the body against pollen.
In clinical practice, there are several possibilities to avoid the
activity of IgE and many pharmaceutical interventions aim to prevent IgE
production and/or make the immune system more tolerant to allergens by
inducing a shift in Th cell responses from Th2 to Th1 or regulatory T
cells 6,7; more recently, the concept of mAbs
targeting and blocking IgE directly has been introduced8. Alternatively, it may be possible to block the
action of IgE indirecty by induction of allergen-specific IgG through
passive 9 or active vaccination10,11. This approach is supported by the clinical
observation that successful specific immunotherapy may correlate with an
increase of the IgG/IgE ratio, and more recently, that polyclonal and
monoclonal allergen specific IgG antibodies were able to curb allergic
immune responses both in mice and humans as a form of passive
vaccination 12-14. Hence, it seems reasonable to
conclude that the overarching goal of immunotherapy should be the
induction of allergen-specific IgG antibodies.
This raises the question of antibody specificity and quality. Which are
the key parameters driving or inhibiting allergic responses? As outlined
below, the answer is complex and different for IgE mediated activation
by allergen versus IgG mediated neutralization of allergen versus
FcγRIIb-mediated inhibition of allergic responses (Figure 1). The same
is true for antibody specificity, as rules for IgE-mediated activation
versus IgG-mediated blockade or FcγRIIb-mediated inhibition are
fundamentally different. Perhaps unexpectedly, the role of IgG
subclasses plays only a minor role in inhibiting the allergic response.