Abstract
It is unclear if allergen immunotherapy (AIT) can reduce allergy effector cell activation. We evaluated the basophil response during Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) and its relationship to allergen-specific immunoglobulin G4 (sIgG4) in allergic rhinitis and/or asthma patients. The study included 55 subjects, of which 35 cases received Der p SCIT and 20 controls received standard medications. Symptom and medication scores (SMSs), sIgG4 levels, specific immunoglobulin E (sIgE) levels, allergen-induced basophil activation tests (BATs) in whole blood, and BAT inhibition assays in serum were determined at weeks 0, 4, 12, 16, 52, and 104 of SCIT. Levels of Der p sIgG4 in SCIT patients significantly increased after 12 weeks of treatment compared to week 0. Serum obtained from SCIT patients significantly inhibited basophil activation after 12 weeks of treatment. Removal of immunoglobulin G4 (IgG4) antibodies at week 104 reduced the ability of serum to block basophil activation. An increase of Der p sIgG4 rather than reduction of Der p sIgE correlated with the reduction of basophil activation during SCIT. The sIgG4 antibodies may compete with sIgE binding to allergens to form an immunoglobulin E (IgE)–allergen complex. SCIT reduced the sensitivity of allergen-triggered basophil activation in Der p allergic rhinitis and/or asthma patients through induction of sIgG4.
Highlights
Allergen-specific immunotherapy (AIT) is an effective treatment for many allergens including house dust mite allergens (Wang et al, 2006; Durham et al, 2012; Nelson, 2014), which are a major cause of allergic rhinitis and allergic asthma in China (Li et al, 2009)
We investigated the relationship between basophil response and immunoglobulin G4 (IgG4) antibodies to demonstrate that Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) might reduce basophil reactivity and/or sensitivity through induction of IgG4 in dust mite–sensitive subjects
The combined symptom medication score (SMS) of asthma and rhinitis decreased significantly after 12 weeks of treatments compared to baselines in both groups (Supplementary Figure S1A), with more significant declines seen in the SCIT subjects compared to medication-treated subjects at weeks 52 and 104 (Supplementary Figure S1A)
Summary
Allergen-specific immunotherapy (AIT) is an effective treatment for many allergens including house dust mite allergens (Wang et al, 2006; Durham et al, 2012; Nelson, 2014), which are a major cause of allergic rhinitis and allergic asthma in China (Li et al, 2009). AIT-Induced HDM-IgG4 Reduces Basophil Activation responses are involved in the induction of allergen-specific immunoglobulin G (IgG) antibodies, in particular, IgG4 antibodies. IgG4 antibodies may have blocking activities, as they compete with specific immunoglobulin E (sIgE) for binding to the allergen. This inhibits allergen–immunoglobulin E (IgE) complex formation on sIgE receptor–expressing cells such as mast cells and basophils. In a peanut immunotherapy study, Santos et al found that depletion of IgG4 reduced the inhibitory effect of peanut-induced basophil activation (Santos et al, 2015). We investigated the relationship between basophil response and IgG4 antibodies to demonstrate that Der p SCIT might reduce basophil reactivity and/or sensitivity through induction of IgG4 in dust mite–sensitive subjects
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