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.