The association between specific IgE antibodies to component allergens and allergic symptoms on dog and cat exposure among Korean pet exhibition participants.

Background: Component resolved diagnostics (CRD) in dog and cat allergy is not sufficiently investigated, especially regarding new components such as Can f 4, Can f 6, and Fel d 7. The purpose of this study is to evaluate the potential role of CRD with new components in predicting allergic symptoms on dog and cat exposure. Methods: Among 552 Korean adults who participated in a pet exhibition and completed questionnaires regarding exposure to dog or cat and allergic symptoms, 522 were venipunctured for measurement of IgE and IgG4 antibody concentration against dog and cat dander extract and underwent skin prick test (SPT). In 238 individuals who were sensitized for both dog and cat dander extract, the dog IgE components (Can f 1-6) and the cat components (Fel d 1/2/4/7) were analyzed. Results: An increasing number of sensitizing components was associated with the likelihood of having any allergic symptoms (P < 0.001 for dog and P < 0.01 for cat), and those of asthma (P < 0.01 for dog and P < 0.05 for cat) and rhinoconjunctivitis (P < 0.001 for dog and P < 0.05 for cat). Pairwise correlation of IgE levels was r = 0.56 (P < 0.001) for Can f 6 and Fel d 4, r = 0.74 (P < 0.001) for Can f 1 and Fel d 7 and r = 0.84 (P < 0.001) for Can f 3 and Fel d 2. Conclusions: Polysensitization to dog and cat allergen components is associated with high likelihood of having allergic symptoms during exposure to dogs and cats. Cross-reactivity between dog and cat allergen components is also identified. CRD has a potential in fine-tuning prediction for allergic symptoms on dog and cat exposure.

Allergen-Specific IgE and IgG4 as Biomarkers for Immunologic Changes during Subcutaneous Allergen Immunotherapy.

(1) Background: Biomarkers of efficacy for subcutaneous immunotherapy (SCIT) on allergic rhinitis have not been evaluated in details. The present study aims to assess the relevance of measuring of sIgE, sIgG4 and IgE/IgG4 ratio during SCIT in patients with allergic rhinitis; (2) Methods: 20 patients, 13 men and 7 women aged 19 to 58 years, with clinically manifested seasonal and perennial allergic rhinitis were studied. At the initiation and in the end of the three-year course of SCIT serum allergen-specific IgE and IgG4 were measured with ImmunoCAP system. The sIgE/sIgG4 ratio was calculated as a biomarker for immunologic effectiveness; (3) Results: There was a significant increase of sIgG4 antibodies (p < 0.05), while at the end of SCIT for the sIgE levels no significant changes were seen (p > 0.05). Moreover, 90% of patients showed a decrease of the IgE/IgG4 ratio; (4) Conclusions: In most of treated patients with AR, SCIT with Bulgarian allergen products leads to clear immunological changes. After a 3-year of SCIT there is a significant increase in allergen specific IgG4 levels and both decrease of sIgE and IgE/IgG4 ratio. sIgE, sIgG4 and IgE/IgG4 ratio can be used as a substantial biomarker for predicting immunological effectiveness of SCIT.

Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study.

BACKGROUND: Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described. METHODS: A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes. RESULTS: The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months. CONCLUSIONS: Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT. TRIAL REGISTRATION: UMIN000009373, Multicenter Oral Immunotherapy for Hen's Egg, Cow's Milk, and Wheat-Allergic Children at Outpatient Clinic.

[The secondary prevention effect and influence on serum sIgG4, IL-27 and IL-33 levels of subcutaneous immunotherapy in children with allergic rhinitis and cough variant asthma].

Objective:To observe the secondary prevention efficacy of subcutaneous immunotherapy in children with allergic rhinitis（AR） and cough variant asthma（CVA） and to analyze its effect on the levels of serum sIgG4, IL-27 and IL-33. Method:The clinical data of 112 children aged 5-12 years with AR and CVA were retrospectively analyzed and divided into control group（52 cases） and SCIT group（60 cases）. The patients were followed up for 3 years. The control group was received symptomatic treatment only, and the SCIT group was received SCIT on the basis of the control group. The numbers of cases of the two groups of children who produced new allergens and developed CA were analyze during the 3-year treatment. Changes in serum sIgG4, IL-27, IL-33 levels, TNSS, DCSS, NCSS, TRMS, TCMS, VAS score, and FEV1% before and after treatment were analyzed. Result:During the treatment, 4 patients（6.67%） in the SCIT group produced the new allergen, and 20 patients（38.46%） in the control group（χ²=16.73, P<0.05）. There were only 3 cases（5.00%） in the SCIT group, which developed into CA, while 15 cases（28.85%） in the control group. The difference between the groups was statistically significant（χ²=11.74, P<0.05）. Compared with baseline, serum levels of sIgG4 and IL-27 in both groups were significantly increased after 3 years of treatment（P<0.05）, while serum levels of IL-33 were significantly decreased（P<0.05）. After 3 years of treatment, serum levels of sIgG4 and IL-27 in the SCIT group were significantly higher than those in the control group, and serum levels of IL-33 were significantly lower than those in the control group（P<0.05）. Compared with baseline, TNSS, DCSS, NCSS, TRMS, TCMS, VAS, and FEV1% in both groups were significantly improved at 1, 2, and 3 years of treatment（P<0.05）. There was no significant difference in TNSS, DCSS, NCSS, TRMS, TCMS, VAS and FEV1% between the two groups at baseline（P>0.05）, while after 1, 2 and 3 years of treatment the above indicators in the SCIT group were significantly better than those in the control group（P<0.05）. Conclusion:SCIT treatment can prevent AR with CVA patients from producing new allergens and developing into CA, and improve serum sIgG4 and IL-27 and IL-33 levels.

[Effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4 in patients with allergic rhinitis in Hainan area].

Objective:The aim of this study is to investigate the effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4（sIgG4） in patients with allergic rhinitis （AR） in Hainan area. Method:Seventy-two patients with dust-mite allergic rhinitis, all three generations of whom were local islanders in Hainan, were randomly divided into control group（36 cases） and SLIT group（36 cases）. sIgG4 and sIgE expression levels were detected before treatment, 6 months after treatment, 12 months after treatment, and 18 months after treatment. The patient's symptom score, medication score, VAS score and adverse reactions was also assessed. Finally, through statistical analysis of the relevant data collected at 4 time points in the two groups of patients, the efficacy, safety and changes of sIgG4 antibody expression level in patients with allergic rhinitis receiving sublingual specific immunotherapy in Hainan were observed. Result:Symptoms scores, medication scores and VAS scores were significantly improved in the SLIT group after treatment compared with before treatment（P<0.05）, and serum sIgG4 increased significantly（P<0.01）, serum sIgE showed no significant change（P>0.05）. In the control group, symptom scores, medication scores and VAS scores were also significantly improved compared with before treatment（P<0.05）, while serum sIgG4 and sIgE showed no significant change（P>0.05）. When comparing the two groups, Symptoms scores, medication scores and VAS scores of the SLIT group were significantly lower than those of the control group at 12 months and 18 months after treatment（P<0.05）. sIgG4 expression levels in the SLIT group were significantly higher than those in the control group after 6, 12 and 18 months of treatment（P<0.01）. There was no significant difference in sIgE expression level between the two groups（P>0.05）. No severe systemic adverse reactions occurred in the two groups, and 3 patients showed mild adverse reactions in the SLIT group. Conclusion:Sublingual immunotherapy of Dermatophagoides Farinae was effective and could increase the expression of sIgG4 in patients with Dermatophagoides farinae AR, sIgG4 is expected to be an immunological marker for the objective evaluation of the clinical efficacy of Hapten.

Performance of basophil activation test and specific IgG4 as diagnostic tools in nonspecific lipid transfer protein allergy: Antwerp-Barcelona comparison.

BACKGROUND: Recent studies show that nsLTP sensitization is not limited to the Mediterranean basin and can present diverse clinical phenotypes. It remains challenging to predict clinical outcome when specific IgE antibodies (sIgE) to nsLTPs are present. This study compares both clinical and in vitro allergy characteristics but also diagnostic performance of a basophil activation test (BAT) and sIgG4 in nsLTP-sensitized patients from Antwerp (ANT, Belgium) and Barcelona (BCN, Spain). METHODS: Adult subjects with positive sIgE rPru p 3 and/or rMal d 3 ≥ 0.10 kUA /L (n = 182) and healthy controls (n = 37) were included. NsLTP-sensitized individuals were stratified according to clinical symptoms with peach/apple, respectively. BAT rPru p 3 and rMal d 3 were performed and sIgG4 antibodies to both components quantified. RESULTS: In BCN, only ratios of sIgG4/sIgE rMal d 3 and BAT rMal d 3 (0.001 µg/mL) can identify clinically relevant Mal d 3 sensitization (sensitivity of 60%-63% and a specificity of 75%-67%, respectively). In ANT, only the sIgE/total IgE rPru p 3 ratio shows added value (sensitivity 60% and specificity 83%). Finally, it appears that symptomatic patients in BCN are more sensitive to lower allergen concentrations compared to ANT. In addition, it was shown that ANT patients were more often sensitized to pollen and that specific pollen sources differed between regions. CONCLUSIONS: NsLTP-related allergy profiles and diagnostic performance differ significantly between regions and are component-specific, which makes extrapolation of data difficult to do. In addition, it seems that basophil sensitivity might show geographical differences. Additional research is needed to confirm these findings.

Effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4 in patients with allergic rhinitis in Hainan area / 临床耳鼻咽喉头颈外科杂志

Objective@#The aim of this study is to investigate the effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4（sIgG4） in patients with allergic rhinitis （AR） in Hainan area.@*Method@#Seventy-two patients with dust-mite allergic rhinitis, all three generations of whom were local islanders in Hainan, were randomly divided into control group（36 cases） and SLIT group（36 cases）. sIgG4 and sIgE expression levels were detected before treatment, 6 months after treatment, 12 months after treatment, and 18 months after treatment. The patient's symptom score, medication score, VAS score and adverse reactions was also assessed. Finally, through statistical analysis of the relevant data collected at 4 time points in the two groups of patients, the efficacy, safety and changes of sIgG4 antibody expression level in patients with allergic rhinitis receiving sublingual specific immunotherapy in Hainan were observed. @*Result@#Symptoms scores, medication scores and VAS scores were significantly improved in the SLIT group after treatment compared with before treatment（P<0.05）, and serum sIgG4 increased significantly（P<0.01）, serum sIgE showed no significant change（P>0.05）. In the control group, symptom scores, medication scores and VAS scores were also significantly improved compared with before treatment（P<0.05）, while serum sIgG4 and sIgE showed no significant change（P>0.05）. When comparing the two groups, Symptoms scores, medication scores and VAS scores of the SLIT group were significantly lower than those of the control group at 12 months and 18 months after treatment（P<0.05）. sIgG4 expression levels in the SLIT group were significantly higher than those in the control group after 6, 12 and 18 months of treatment（P<0.01）. There was no significant difference in sIgE expression level between the two groups（P>0.05）. No severe systemic adverse reactions occurred in the two groups, and 3 patients showed mild adverse reactions in the SLIT group. @*Conclusion@#Sublingual immunotherapy of Dermatophagoides Farinae was effective and could increase the expression of sIgG4 in patients with Dermatophagoides farinae AR, sIgG4 is expected to be an immunological marker for the objective evaluation of the clinical efficacy of Hapten.

Effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4 in patients with allergic rhinitis in Hainan area / 临床耳鼻咽喉头颈外科杂志

The aim of this study is to investigate the effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4（sIgG4） in patients with allergic rhinitis （AR） in Hainan area. Seventy-two patients with dust-mite allergic rhinitis, all three generations of whom were local islanders in Hainan, were randomly divided into control group（36 cases） and SLIT group（36 cases）. sIgG4 and sIgE expression levels were detected before treatment, 6 months after treatment, 12 months after treatment, and 18 months after treatment. The patient's symptom score, medication score, VAS score and adverse reactions was also assessed. Finally, through statistical analysis of the relevant data collected at 4 time points in the two groups of patients, the efficacy, safety and changes of sIgG4 antibody expression level in patients with allergic rhinitis receiving sublingual specific immunotherapy in Hainan were observed. Symptoms scores, medication scores and VAS scores were significantly improved in the SLIT group after treatment compared with before treatment（0.05）. In the control group, symptom scores, medication scores and VAS scores were also significantly improved compared with before treatment（0.05）. When comparing the two groups, Symptoms scores, medication scores and VAS scores of the SLIT group were significantly lower than those of the control group at 12 months and 18 months after treatment（0.05）. No severe systemic adverse reactions occurred in the two groups, and 3 patients showed mild adverse reactions in the SLIT group. Sublingual immunotherapy of Dermatophagoides Farinae was effective and could increase the expression of sIgG4 in patients with Dermatophagoides farinae AR, sIgG4 is expected to be an immunological marker for the objective evaluation of the clinical efficacy of Hapten.

Persistent regulatory T-cell response 2 years after 3 years of grass tablet SLIT: Links to reduced eosinophil counts, sIgE levels, and clinical benefit.

BACKGROUND: In the first 2 years of grass tablet sublingual immunotherapy treatment, we have previously demonstrated a progressive development of a regulatory T-cell response, which was preceded by an early decrease in the frequency of both IL-4+ cells and sIgE levels. A progressive increase in sIgG4 levels and FAB blockage were also found. METHODS: By monitoring immunological kinetics during 3 years of active treatment + 2 years of follow-up, we aimed to identify key immunological parameters that could explain sustained clinical benefit of grass tablet sublingual immunotherapy. RESULTS: Thirty patients completed the 5-year clinical trial protocol. Although individual responses were heterogeneous, reduction in both sIgE and circulating IL-4+ cells compared to the initial 1- to 4-month peak was maintained throughout the 3-year treatment period and for 2 years after discontinuation. Meanwhile, after a 2-year increase in sIgG4, the levels were stabilized during the third year and decreased post-therapy. FAB inhibition remained significantly inhibited throughout the study compared to preimmunotherapy in 83% of patients. A sustained regulatory T-cell response, after IT cessation, occurs in two-thirds of the patients. There was a statistical association between this regulatory response, the maintenance of lower eosinophil counts during grass pollen seasons, and sIgE titers lower than before immunotherapy treatment, and the latter were significantly associated with clinical response. CONCLUSION: Our results suggest that the immunological mechanisms underlying the sustained response after 2 years of cessation of immunotherapy (3-year treatment period) are linked to the acquisition and maintenance of a regulatory T-cell response.

Development of a microarray-based method for allergen-specific IgE and IgG4 detection.

BACKGROUND: sIgE and sIgG4 detection is necessary for more accurate and effective type I hypersensitivity diagnostics and the estimation of disease development. Typically, the analyses of these antibodies are performed separately with the help of various specialized systems. The aim of this study was to develop a microarray-based method for the simultaneous quantitative detection of sIgE and sIgG4 to the most common allergens in a single sample. METHODS: A quantitative method for the simultaneous detection of sIgE and sIgG4 was developed based on the technology of hydrogel microchips previously designed at Engelhardt Institute of Molecular Biology, Russian Academy of Sciences (EIMB RAS). The microarray contained gel pads with immobilized allergens and gel pads that allow for the obtaining of sIgE and sIgG4 internal calibration curves for each allergen during the assay. The possibility of the simultaneous detection of sIgE and sIgG4 was developed using the corresponding Cy5 and Cy3 fluorescent dyes. RESULTS: The multiplex immunoassay method using hydrogel microarrays developed in this study allowed the quantitative detection of sIgE and sIgG4 to 31 allergens from different groups in a single assay. A comparison of the microarray with the existing plate-based analogues (i.e., ALLERG-O-LIQ and sIgG4 ELISA) was performed by analysing 152 blood serum samples and by evaluating Pearson correlation coefficients, ROC analysis, and Passing-Bablok linear regression results. CONCLUSION: The implementation of this method in allergy diagnostics will provide the possibility of simultaneously performing primary patient screening and obtaining additional information concerning the severity of the allergies and the choice of an appropriate therapy.

Relationship of dog- and cat-specific IgE and IgG4 levels to allergic symptoms on pet exposure.

BACKGROUND: Environmental allergens may induce the generation of allergen-specific IgE (sIgE) and IgG4 (sIgG4). Some studies report an association of sIgG4 to protection against allergic symptoms after exposure to the relevant allergen. OBJECTIVE: We examined the relationship of dog and cat sIgE and sIgG4 levels to self-reported allergic symptoms on pet contact. METHODS: Participants 18 years of age in the Detroit Childhood Allergy Study cohort were asked whether they experienced symptoms on exposure to cats and dogs. Serum was assayed for cat and dog sIgE and sIgG4. Geometric means, ratios of cat and dog sIgE, sIgG4, and ratios of sIgG4/sIgE were compared between symptomatic and asymptomatic teens with the use of Wilcoxon rank sum tests. Ratios of sIgG4/sIgE, adjusted for presence of sIgE (≥0.35 kU/mL), were analyzed with logistic regression. RESULTS: Data on 500 participants were analyzed. Compared with asymptomatic teens, teens symptomatic with cat exposure had higher cat sIgE, sIgG4, and lower ratio of sIgG4/sIgE. Teens symptomatic after dog exposure had higher dog sIgE levels and lower sIgG4/sIgE, but similar levels of sIgG4 compared with asymptomatic participants. Increasing cat and dog sIgG4/sIgE ratios were associated with a lower likelihood of reporting allergic symptoms (cat: adjusted odds ratio, 0.8; 95% CI, 0.6-0.9; dog: adjusted odds ratio, 0.8; 95% CI, 0.7-1.0). CONCLUSION: sIgG4 levels to cat and dog allergens correlate with lower rates of pet-induced allergic symptoms when interpreted in the context of concomitant sIgE. However, sIgG4 appears to have little utility as an isolated marker to indicate that pet exposure will be well tolerated.