Specific IgE and IgG4 Profiles of House Dust Mite Components in Allergen-Specific Immunotherapy

Abstract

BackgroundAllergen immunotherapy (AIT) can induce immune tolerance to allergens by activating multiple mechanisms, including promoting IgG4 synthesis and blunting IgE production. However, the longitudinal data of sIgE and sIgG4 to allergen components during AIT are limited.ObjectiveWe sought to investigate the persistence and evolution of sIgE and sIgG4 against house dust mite (HDM) components during AIT and explore their correlation with clinical responses.MethodsSixty allergic rhinitis (AR) with/without asthma patients receiving AIT for HDM were enrolled in AIT group. Thirty AR patients without receiving AIT served as control group. Blood samples were collected for sIgE, sIgG4 to HDM components (Derp 1, Derf 1, Derp 2, Derf 2, Derp 7, Derp 10, Derp 21 and Derp 23) assay at baseline, Month 6 and Month 18 of AIT. Combined symptom and medication scores (CSMS) were obtained accordingly.ResultsIn the AIT group, sIgG4 to the HDM components of Derp 1, Derf 1, Derp 2 and Derf 2, Derp 21 significantly increased at Month 18 compared to the baseline (36.2 UA/mL vs 158.8 UA/mL, 46.4 UA/mL vs 94.6 UA/mL, 80.5 UA/mL vs 152.3 UA/mL, 78.3 UA/mL vs 205.1 UA/mL, 42.3 UA/mL vs 59.3 UA/mL, all p<0.05), sIgE to HDM components didn’t see differences at baseline and at Month 18 (all p>0.05).The numbers of positive HDM component sIgE and sIgG4 increased from 4.5 to 5 and 0 to 1.5 respectively (both p<0.05). However, the changes of sIgE, sIgG4, sIgE/sIgG4 ratio and the numbers of positive HDM components had no correlations with the improvement of CSMS after AIT (all ρ<0.3). For the control group, the sIgE and sIgG4 did not change significantly during the observational period (all p>0.05).ConclusionAIT can induce the production of sIgG4 to HDM components. However, the increased sIgG4 levels of HDM component do not correlate with the corresponding sIgE levels at baseline or with AIT response. sIgG4 to HDM components do not qualify as a biomarker to evaluate the efficacy of AIT.

IgE and IgG4 Epitopes of Dermatophagoides and Blomia Allergens before and after Sublingual Immunotherapy

“…Besides IgE, we were particularly interested in the identification of IgG4 epitopes induced during AIT. The observed increase in IgG4 binding to HDM peptides/epitopes as well as in IgG4 amplitude during SLIT in our study is in line with previous observations of increased allergen-specific IgG4 levels during immunotherapy for house dust mite as well as other allergen sources [ 13 , 14 , 38 ].…”

“…There is a plethora of literature that evaluates molecular profiles of IgE and IgG4 recognition during AIT [ 13 , 14 ], especially subcutaneous. Epitope mapping goes back approximately 30 years [ 15 ], some previous works have identified epitopes in HDM allergens, such as Der p 5 [ 16 ], Der p 7 [ 17 ], Der p 2 [ 18 , 19 ], Der p 39 [ 20 ], and Blo t 11 [ 21 ] to characterize IgE only or IgE and IgG binding sites by various methods.…”

Pre-pubertal sublingual immunotherapy is more effective than immunotherapy during puberty in allergic rhinitis and asthma

“…Patients with allergic rhinitis and dust mite allergy who received SLIT showed a shift from Th2 to Th1 mode, with a decrease in the levels of Th2-secreting cytokines in peripheral blood mononuclear cells (IL-4, IL-5, IL-13) [23]. Secondly, SLIT can consistently reduce allergen-speci c IgE synthesis and contribute to the ongoing production of IgG4-blocking antibodies [24]. A multicenter randomized controlled open trial found that after 12 months of treatment, patients in the SLIT group showed a signi cant increase in serum-speci c IgG4 levels compared to controls, while the IgE/IgG4 ratio showed a signi cant decrease compared to baseline [25].…”

Mechanisms and biomarkers of successful allergen-specific immunotherapy

“…This change is accompanied by induced blocking antibodies (particularly, of the subclass IgG4) [ 107 ]. The sIgE/tIgE ratio is often increased following AIT treatment [ 108 109 110 111 112 ], however, no changes are observed when evaluated less than 2 years of AIT treatment [ 113 ]. The blocking activity of IgG antibodies maintains unchanged for at least 2 years of discontinuation of AIT, despite the reduction in the IgG1 and IgG4 levels [ 114 ], suggesting long-term immune tolerance following cessation of AIT treatment.…”