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.