On the role of allergen-specific IgG subclasses for blocking human basophil activation

Abstract

Successful treatment of IgE mediated allergies by allergen-specific immunotherapy (AIT) usually correlates with the induction of allergen-specific IgG4. However, it is not clear whether IgG4 prevents the allergic reaction more efficiently than other IgG subclasses. Here we aimed to compare allergen-specific monoclonal IgG1 and IgG4 antibodies in their capacity to inhibit type I allergic reactions by engaging FcγRIIb. We found that IgG1, which is the dominant subclass induced by viruses, binds with a similar affinity to the FcγRIIb as IgG4 and is comparable at blocking human basophil activation from allergic patients; both by neutralizing the allergen as well as engaging the inhibitory receptor FcγRIIb. Hence, the IgG subclass plays a limited role for the protective efficacy of AIT even if IgG4 is considered the best correlate of protection, most likely simply because it is the dominant subclass induced by classical AITs.

The next generation virus‐like particle platform for the treatment of peanut allergy

“…neutralizing IgG antibodies [25][26][27] and that these antibodies can block IgE-mediated antigen presentation in a competitive high affinity and epitope-specific manner. In addition, it has been shown in murine models of cat or peanut allergies that the transfer of allergen-specific IgG induced by allergy vaccination resulted in protection against local and systemic allergen challenge 28,29 in a noncompetitive low affinity pathway via inhibitory FcγRIIb activation.…”

Bacterial expression systems based on Tymovirus-like particles for the presentation of vaccine antigens

“…Modern solutions in allergy treatment now include not only widely described allergen-specific IgE-targeted treatments but also novel allergen-specific IgGs, which are possible key effectors for so-called next-generation immunotherapy when allergens are displayed on the VLP surface ( Schmitz et al, 2009 ; Bachmann et al, 2020 ). A recent paper underlines that specific IgG subclasses play a minor role in allergy-specific immunotherapy ( Zinkhan et al, 2022 ).…”

“…Modern solutions in allergy treatment now include not only widely described allergenspecific IgE-targeted treatments but also novel allergen-specific IgGs, which are possible key effectors for so-called next-generation immunotherapy when allergens are displayed on the VLP surface (Schmitz et al, 2009;Bachmann et al, 2020). A recent paper underlines that specific IgG subclasses play a minor role in allergyspecific immunotherapy (Zinkhan et al, 2022). It has been emphasized that strong activators of antigen presenting cells (APC) such as VLPs are recognized by so-called pathogen recognition receptors (PRRs) expressed on the surface of antigen-presenting cells (APCs).…”

On the role of antibody affinity in the IgE mediated allergic response

“…Hence, it is generally assumed that IgG4 is the key IgG subclass for clinical outcome. However, as pointed out previously, the correlation between clinical efficacy and IgG4 may simply be due to the fact that the way we are currently performing immunotherapy is preferentially inducing IgG4 rather than other subclasses 27 ; mostly due to the absence of strong toll-like receptor or other innate ligands in the formulations. It should be noted that a correlation between clinical outcome and allergen-specific IgG4 has been reported in some but not all studies.…”