7. CD23 in current allergy therapy approaches
As long as the biology of CD23 is not completely understood, the potential use for CD23 as a therapeutic target is limited. However, several recent studies have begun to shed light on how current allergy therapies affect CD23.
The only disease modifying therapy for allergies is allergen-specific immunotherapy (AIT) (94,95). Multiple injections of increasing allergen doses induce the generation of tolerance via regulatory T cells and the induction of protective IgG4 antibodies (96, 97). The role of CD23 in the generation of such IgG responses is unclear. However, the tolerogenic IgG induced by AIT was shown to inhibit IgE binding to CD23 and hence antigen presentation by EBV-transformed B cells (98 –100).
A different approach to treat allergic diseases is by anti-IgE therapy (101). Omalizumab, a monoclonal anti-IgE antibody is used for severe allergic asthma and chronic spontaneous urticaria (102,103). Mechanistically, Omalizumab, inhibits both FcεRI:IgE and CD23:IgE interactions (104). A more recent anti-IgE antibody, Ligelizumab, was shown to display increased efficacy in the treatment of allergic asthma (105). Functionally, Ligelizumab was shown to display reduced IgE:CD23 inhibition compared to Omalizumab but enhanced inhibition of IgE:FcεRI binding (106). A different anti-IgE antibody referred to as MEDI4212 is mimicking CD23 binding to IgE and was shown to inhibit allergic responses in mice and inhibit the FcɛRI pathway (63). A further interesting anti-IgE termed (8D6), an anti-IgE Fab bound to IgE-Fc through a mixed protein-carbohydrate epitope, was shown to inhibit FcεRI while retaining CD23 binding (107,108). The monoclonal anti-CD23 antibody Lumiliximab, which specifically targets CD23 was shown to inhibit allergen-induced response in allergen-presenting cells and reduced Th2 response (109). However, anti-CD23 never lead to particularly significant clinical outcomes in patients with asthma suggesting that blocking CD23 does not reduce allergic symptoms. Hence, studying the type of immune response elicited by CD23 is an essential to understanding its role in allergy and immunotherapy as it could very well be of benefit to target IgE towards the CD23 pathway instead of blocking this interaction.
Conclusion
The general goal of disease-modifying allergy immunotherapy is to reduce IgE responses while enhancing IgG and regulatory T cell responses. While evidence from experimental disease models as well as allergic patient studies on CD23 are lacking, evidence shows that i) CD23 can absorb and clear IgE from the serum in non-inflammatory fashion ii) CD23 reduces the synthesis of IgE from B cells iii) CD23 facilitates antigen-specific IgG and T cell responses (Fig. 4). Together, those factors lead us to believe that CD23 deserves a closer look as a therapeutic target in allergies.