Functional and Immunoreactive Levels of IgG4 Correlate with Clinical Responses during the Maintenance Phase of House Dust Mite Immunotherapy

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 Dermatophagoides pteronyssinus s.c. allergen immunotherapy (SCIT) in allergic rhinitis and/or asthma patients. Combined symptom medication scores (SMS), D. pteronyssinus -sIgG4 levels, D. pteronyssinus -sIgE levels, and the serum inhibitory capacity agains D. pteronyssinus -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 ( p < 0.05). Levels of D. pteronyssinus -sIgG4 in SCIT patients showed a significant increase from week 12 to 156 ( p < 0.05). Serum obtained from SCIT patients significantly inhibited D. pteronyssinus -sIgE binding to B cells after 16 wk ( p < 0.01). Significantly lower levels of D. pteronyssinus -sIgE were observed in SCIT patients after 52 wk ( p < 0.05). A significant relationship was demonstrated between SMS and IgE-FAB or D. pteronyssinus -sIgG4 during the maintenance phase according to linear regression analysis. In conclusion, D. pteronyssinus -sIgG4 level and D. pteronyssinus 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.