Changes in BAT with immunomodulatory treatments
As basophils express FceRI and bear IgE, they are an effector cell of
interest to explore the long-term effects of
immunotherapy74; the suppressive effects of blocking
antibodies induced during treatment. A change in basophil sensitivity
during the first three weeks of allergen immunotherapy correlated
strongly with the clinical effect of treatment during the first
year42 as well as three years of
treatment45 and could be developed into a diagnostic
biomarker for allergen immunotherapy. Passive sensitization approaches
in which pre and post-treatment plasma are used to sensitize primary
basophils or to pre-incubate with allergen prior to adding sensitized
cells are ways to assess the function and suppressive effects of
post-treatment plasma containing blocking
antibodies62,75,76. Another experimental setup that
can be used to explore the effects of blocking antibodies is the washed
BAT, in which plasma surrounding basophils is removed, and its
comparison with whole blood BAT42. Typically,
post-treatment plasma contain allergen-specific antibodies of different
isotypes to IgE, namely IgG and IgA, that compete with IgE for allergen
binding reducing the amount of allergen that is able to cross-link IgE
antibodies on the surface of mast cells and basophils and therefore
reducing the chance of inducing an allergic reaction or its
severity77. Evidence that blocking antibodies can
induce inhibitory cell signalling through ITIM-coupled receptors is
lacking in natural tolerance or desensitization through
IT78. The use of specific inhibitors of signalling
molecules downstream the high-affinity IgE receptor can help to confirm
whether observed effects of treatment are IgE-mediated.
BAT has also shown to be useful in monitoring the response to treatment
with omalizumab47,79-81. In a peanut study, the BAT
was used to make decisions about the need to adjust the dose of
omalizumab82. Given that the anti-IgE antibody
captures IgE in circulation and reduces the IgE that is bound to
receptors on the surface of circulating basophils and tissue mast cells,
it leads to a progressive reduction in surface expression of FceRI on
effector cells, and in response to the allergen in vitro in the
BAT47,48,83. However, because the reduction in
receptor density on the surface of these effector cells enhances their
intrinsic sensitivity84, omalizumab can paradoxically
increase basophil reactivity to the allergen. As a result, the patients
that are most likely to better respond to omalizumab are the one with
higher allergen specific activity, i.e. the ones whose proportion of IgE
that is allergen-specific is higher85,86. BAT can
potentially be useful in monitoring the clinical response to other
biologicals in terms of their effect on the risk of acute reactions to a
given allergen.