Allergen-specific immunotherapy for house dust mite allergy is effective, but there are no validated biomarkers reflecting or predicting the clinical efficacy. We aimed to investigate the relationship between clinical outcomes and functional responses of allergen-specific IgG4 (sIgG4) and specific IgE (sIgE) during s.c. allergen immunotherapy (SCIT) in allergic rhinitis and/or asthma patients. Combined symptom medication scores (SMS),-sIgG4 levels, -sIgE levels, and the serum inhibitory capacity against-sIgE facilitated allergen binding to B cells (IgE-FAB) were determined during the updosing (week 0, 4, 12, and 16) and maintenance (week 52, 104, and 156) phase of SCIT. We found that SCIT patients had a significant improvement in SMS from week 52 to 156 compared with medication-treated control subjects ( < 0.05). Levels of -sIgG4 in SCIT patients showed a significant increase from week 12 to 156 ( < 0.05). Serum obtained from SCIT patients significantly inhibited -sIgE binding to B cells after 16 wk ( < 0.01). Significantly lower levels of -sIgE were observed in SCIT patients after 52 wk ( < 0.05). A significant relationship was demonstrated between SMS and IgE-FAB or -sIgG4 during the maintenance phase according to linear regression analysis. In conclusion,-sIgG4 level and IgE-FAB are associated with clinical efficacy in the maintenance phase rather than the updosing phase of SCIT. Immunologic tolerance can be induced with SCIT when maintenance phase is achieved.

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.

<b><i>Background:</i></b> Few studies have directly compared the immunologic responses to specific subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). <b><i>Objective:</i></b> We aimed to directly compare clinical efficacy and immunological responses between SLIT and SCIT in allergic rhinitis (AR) sensitized to house dust mites. <b><i>Methods:</i></b> Sixty-seven patients (age 5–55 years) with moderate-severe <i>Dermatophagoides pteronyssinus</i> (Der-p) and <i>Dermatophagoides farinae</i> AR with or without asthma were randomized (2:2:1) into SLIT (<i>n</i> = 27), SCIT (<i>n</i> = 26) and placebo (<i>n</i> = 14) groups. Symptom and medication scores, visual analogue score, serum Der-p specific immunoglobulin G4 (Der-p-sIgG4), CD4⁺CD25⁺FoxP3⁺ regulatory T cells (Tregs) and serum cytokines were measured. <b><i>Results:</i></b> After 1-year treatment, a significant improvement of total rhinitis score (TRS), total rhinitis medication score (TRMS) and visual analogue score occurred in both SLIT and SCIT. There were no differences in clinical efficacy except for TRMS (<i>p</i> = 0.026) when SLIT and SCIT were directly compared. CD4⁺CD25⁺FoxP3⁺ Tregs had a trend towards upregulation in the 2 modes and inversely correlated with TRS (<i>p</i> = 0.024) only in SLIT. Der-p-sIgG4 significantly increased in SLIT and SCIT (<i>p</i> &#x3c; 0.05), and it was 30 times higher in SCIT than SLIT after the treatment (<i>p</i> &#x3c; 0.05). Serum interferon-γ significantly increased only in SCIT after 1 (<i>p</i> = 0.008), 6 (<i>p</i> = 0.007) and 12 (<i>p</i> = 0.008) months of treatment and inversely correlated with TRS (<i>p</i> = 0.032). <b><i>Conclusion:</i></b> While SCIT and SLIT have similar rates of clinical improvement, the 2 modes reveal heterogeneous changes of CD4⁺CD25⁺Foxp3⁺ Tregs, sIgG4 and cytokines.