The Functional IgE-Blocking Factor Induced by Allergen-Specific Immunotherapy Correlates with IgG4 Antibodies and a Decrease of Symptoms in House Dust Mite-Allergic Children.

BACKGROUND: At present, there are no validated biomarkers reflecting or predicting the clinical efficacy of allergen-specific immunotherapy (AIT) . We aimed to investigate the correlations between clinical and immunological responses of patients undergoing house dust mite (HDM) AIT. METHODS: Sixty-nine children diagnosed with HDM allergic rhinitis and/or asthma received standardized Dermatophagoides pteronyssinus (Dp) subcutaneous AIT for 12 months. Twenty HDM-allergic children served as an open control group. Clinical symptom and medication scores were recorded and Dp-specific IgE, IgG4 and IgE-blocking factor were measured before AIT and after 4 and 12 months of AIT. RESULTS: Symptom scores decreased after 4 months and continued to decrease during 12 months of AIT. No differences in medication scores were observed between AIT and the control group during the study period. Levels of Dp IgG4 increased after 4 months and correlated to symptom scores at 12 months (r = -0.296, p = 0.013) of AIT. The Dp IgE-blocking factor increased after 4 months of AIT, and correlated with symptom scores at 4 months (r = -0.307, p = 0.010) and 12 months (r = -0.288, p = 0.016) of AIT. A strong correlation between Dp IgE-blocking factor and Dp IgG4 during AIT (4 months: r = 0.680; 12 months: r = 0.636, both p < 0.0001) was observed. Patients with IgE-blocking factor ≥0.2 after 4 months of AIT showed lower symptom scores at 12 months of AIT (p = 0.0093). CONCLUSIONS: Subcutaneous HDM AIT results in a decrease of allergic symptoms among HDM-allergic children. IgE-blocking activity increased after 4 months of AIT and correlated with clinical symptoms. A high IgE-blocking factor at an early stage of AIT is associated with fewer symptoms at a later stage of AIT.

Effects of sublingual immunotherapy for Dermatophagoides farinae on Th17 cells and CD4(+) CD25(+) regulatory T cells in peripheral blood of children with allergic asthma.

BACKGROUND: Sublingual immunotherapy is becoming a more common treatment for allergic diseases, particularly in pediatric clinics. This type of treatment is highly effective for Dermatophagoides farinae allergy, but the mechanisms resulting in immune tolerance have not been investigated. We explored the effects of sublingual immunotherapy with D. farinae drops on populations of subsets of T immune cells, specifically Th17 cells and CD4(+) CD25(+) regulatory T cells (Treg cells), in peripheral blood of children with allergic asthma. METHODS: We assessed immune cell populations in 60 patients allergic to D. farinae who were randomly divided into 2 groups: a treatment group (n = 30) and a control group (n = 30), treated with sublingual administration of D. farinae drops or placebo, respectively, for 48 weeks. Clinical symptoms of asthma were scored for each individual before and after treatment, and the percentages of Th17 cells and CD4(+) CD25(+) Treg cells in the peripheral blood were evaluated by flow cytometry at 12-week intervals beginning at baseline. RESULTS: Both the mean daily symptom scores and percentages of Th17 cells significantly declined in the treatment group throughout the study period (p < 0.05), and in the control group both declined but without significant differences between time points. In contrast, the percentages of Treg cells significantly increased in the treatment group throughout the study period (p < 0.05), but no statistical difference was observed among different sampling times. CONCLUSION: Sublingual administration of D. farinae drops alters T immune cell profiles and reduces asthma symptoms, likely resulting in enhanced immunosuppression in children with asthma.

[Long-term efficacy of sublingual immunotherapy with Dermatophagoides Farianae Drops in children with allergic asthma sensitized to dust mites].

OBJECTIVE: To observe the efficacy of sublingual immunotherapy (SLIT) in children with allergic asthma during the treatment and 1 year after the treatment. METHOD: This is an open and retrospective study; 80 children with mild-moderate allergic asthma between 4 and 14 years of age were chosen from the Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University from May to August, 2009. All children were sensitized to Dermatophagoides Farianae and/or Dermatophagoides Pteronyssinus and have received anti-asthma drug therapy for 3 months (baseline). Thirty-nine children in SLIT group underwent 2-year SLIT and combined with anti-asthma drug, these children were then followed up for 1 year. Forty-one children in drug group only received anti-asthma drug and were followed up for 3 years. The scores of asthma symptom, scores of asthma medication and the number of discontinuation of anti-asthma drug were compared between the SLIT group and drug group for the baseline, end of the 2nd year and 3rd year treatment. The frequency of acute attack of asthma was also compared between the two groups for 1 year before the treatment and the 3rd year treatment. RESULT: (1) At baseline, the asthma symptom scores, the medication scores and the frequency of acute attack of asthma in 1 year before the treatment of the two groups showed no significant difference. (2) After 2-year SLIT, the daytime asthma symptom scores of SLIT group were lower than the drug group (0.18 ± 0.06,0.93 ± 0.12,Z = -4.873, P < 0.05), the night asthma symptom scores of the two groups showed no significant difference. One year after SLIT, the daytime and night asthma symptom scores of SLIT group were both lower than those of the drug group (daytime SLIT group vs. Drug group: 0.18 ± 0.06 vs. 1.46 ± 0.72,Z = -5.082, P < 0.05;night SLIT group vs. Drug group: 0.05 ± 0.04 vs. 0.66 ± 0.14,Z = -4.019, P < 0.05). (3) At the end of SLIT and 1 year after SLIT, the medication scores of SLIT group were both lower than those of the drug group (End of SLIT SLIT group vs. Drug group: 0.31 ± 0.07 vs. 0.75 ± 0.12,Z = -2.813, P < 0.05;1 year after SLIT SLIT group vs. Drug group: 0.17 ± 0.06 vs. 0.87 ± 0.17,Z = -4.106, P < 0.05), the number of discontinuation of anti-asthma drug of SLIT group were both more than the drug group (End of SLIT SLIT group vs. Drug group: 20 vs. 10,χ(2) = 6.167, P < 0.05;1 year after SLIT SLIT group vs. Drug group: 29 vs.13,χ(2) = 14.581, P < 0.05).(4) In the 3rd year, the frequency of acute attack of asthma in SLIT group was significantly lower than that of drug group (0.69 ± 1.20, 1.20 ± 1.44,Z = -1.968, P < 0.05) . CONCLUSION: SLIT can significantly improve the symptoms of asthma, reduce the use of anti-asthma drug and reduce the frequency of the acute attack of asthma. Meanwhile, the efficacy could still maintain 1 year after the SLIT treatment.

Correlation between serum H2S and pulmonary function in children with bronchial asthma.

Endogenous hydrogen sulfide (H2S) has generated recent research interest because of its potential function as an inflammatory mediator. Despite its apparent functions in vascular smooth muscle, an important player in airway remodeling in asthma, little research has been done to assess the role of H2S in the pathogenesis of asthma. To determine whether serum H2S concentration is correlated with pulmonary function in children with asthma, we measured serum H2S concentration and pulmonary function indices (FVC, FEV1, PEF, FEF25-75, MEF50 and MEF25) in 64 children with asthma and 60 healthy children. Pearson's correlation was used to determine the relationship between serum H2S concentration and lung function parameters. Compared to healthy children, both serum H2S concentration and all lung function parameters were significantly decreased in children with asthma (P<0.05). Furthermore, serum H2S concentration was positively correlated with lung function indices (P<0.05). Thus, decreasing levels of H2S in the serum may be used to indicate decreasing lung function. Further investigation into the causality behind these findings is required.