sIgE Levels Research Articles

Serological analysis of allergic components of house dust mite provides more insight in epidemiological characteristics and clinical symptom development in North China.

House dust mite (HDM) is the most common airborne source causing complex allergy symptoms. There are geographic differences in the allergen molecule sensitization profiles. Serological testing with allergen components may provide more clues for diagnosis and clinical management. This study aims to investigate the sensitization profile of eight HDM allergen components in a large number of patients enrolled in the clinic and to analyze the relation of gender, age, and clinical symptoms in North China. The 548 serum samples of HDM-allergic patients (ImmunoCAP® d1 or d2 IgE ≥0.35) were collected in Beijing City and divided in four different age groups and three allergic symptoms. The specific IgE of HDM allergenic components, Der p 1/Der f 1, Der p 2/Der f 2, Der p 7, Der p 10, Der p 21, and Der p 23, was measured using the micro-arrayed allergen test kit developed by Hangzhou Zheda Dixun Biological Gene Engineering Co., Ltd. The new system was validated by comparing to single-component Der p 1, Der p 2, and Der p 23 tests by ImmunoCAP in 39 sera. The epidemiological study of these IgE profiles and the relation to age and clinical phenotypes were analyzed. A greater proportion of male patients was in the younger age groups, while more female patients were in the adult groups. Both the sIgE levels and the positive rates (approximately 60%) against Der p 1/Der f 1 and Der p 2/Der f 2 were higher than for the Der p 7, Der p 10, and Der p 21 components (below 25%). The Der f 1 and Der p 2 positive rates were higher in 2-12-year-old children. The Der p 2 and Der f 2 IgE levels and positive rates were higher in the allergic rhinitis group. The positive rates of Der p 10 increased significantly with age. Der p 21 is relevant in allergic dermatitis symptom, while Der p 23 contributes to asthma development. HDM groups 1 and 2 were the major sensitizing allergens, with group 2 being the most important component relevant to respiratory symptoms in North China. The Der p 10 sensitization tends to increase with age. Der p 21 and Der p 23 might be associated with the development of allergic skin disease and asthma, respectively. Multiple allergen sensitizations increased the risk of allergic asthma.

Soy Gly m 8 sIgE Has Limited Value in the Diagnosis of Soy Allergy in Peanut Ara h 2-Sensitized Adults

Introduction: Recently, specific IgE (sIgE) sensitization against Gly m 8 (soy 2S albumin) has been described as a good diagnostic marker for soy allergy (SA). The aim of this study was to evaluate the diagnostic value of Gly m 8 by determining the sensitization profiles based on the homologues soy allergens Bet v 1, Ara h 1, Ara h 2, and Ara h 3. Methods: Thirty soy-allergic adults were included; sIgE to total soy extract, Gly m 8, Gly m 4, Gly m 5, Gly m 6, Bet v 1, Ara h 1, Ara h 2, and Ara h 3 were determined. Sensitization patterns were analyzed and determined. The clinical relevance of sIgE of Gly m 8 sensitization was measured by assessing its capacity to degranulate basophils in Gly m8-sensitized patients by an indirect basophil activation test (iBAT). Results: Based on the sIgE patterns of sensitization, two groups of SA patients were identified: (i) peanut-associated SA group (all patients were sensitized to one or more of the peanut compounds) and (ii) non-peanut/PR-10-associated SA group (22 patients were sensitized to Gly m 4 and Bet v 1 but not to any of the peanut compounds). A high and significant correlation between total soy extract and Gly m 6 (R2 = 0.97), Gly m 5 (R2 = 0.85), and Gly m 8 (R2 = 0.78) was observed. A nonsignificant correlation was observed between the levels of sIgE of Gly m 8 versus Ara h2. The iBAT results showed that Gly m 8 did not induce basophil degranulation in any of the peanut-associated patients, indicating that the Gly m8 sensitizations were not clinically relevant. Conclusions: Gly m 8 was not a major allergen in the selected soy-allergic population. The iBAT results indicated that Gly m 8 was not able to induce basophil degranulation in sIgE Gly m 8-sensitized soy-allergic patients. Thus, Gly m 8 would have no added value in the diagnosis of SA in the present study population.

Preanalytical temperature and storage stability of specific IgE antibodies in serum

Allergen-specific serum immunoglobulin E (sIgE) levels are a cornerstone in allergy diagnostics. While immunoglobulins are known to be relatively stable molecules, the influence of preanalytical factors on the stability of sIgE is not thoroughly investigated. We studied the effect of several preanalytical factors: (1) delayed centrifugation of serum samples in tubes with separating gel for 10, 24 and 48 h, (2) prolonged storage at 5 °C for 3, 7, 10 and 14 days, (3) storage tube type (primary tube with separating gel or secondary tube), (4) repeated freeze-thawing cycles, and (5) prolonged storage at −20 °C for 4 and 8 weeks. We found that sIgE is stable at room temperature for 48 h before centrifugation and for 10 days at 5 °C after centrifugation. There was no effect of the separating gel after storing serum for 1 week in the freezer. However, storage for 4–8 weeks, and introducing more than one freeze-thaw cycle resulted in a larger variation of sIgE levels. In conclusion, we found that sIgEs are stable under various preanalytical conditions, which allows for flexible handling of samples for a comprehensive portfolio of sIgE analyses.

Study on the Mechanism of Allergic Rhinitis Based on the Expression of FIB, PCT, hs-CRP, and Th17/Treg-IL10/IL-17 Axis Balance.

The pathogenesis of allergic rhinitis (AR) is ambiguous, while it is clear that various immune cells and cytokines play crucial roles in its occurrence and development. To investigate the effect of exogenous interleukin-10 (IL-10) on the expression of fibrinogen (FIB), procalcitonin (PCT), hypersensitive C-reactive protein (hs-CRP), and Th17/Treg-IL10/IL-17 axis balance in the nasal mucosa of rats with AR. In this study, 48 female-specific pathogen-free Sprague-Dawley rats were randomly divided into 3 groups: blank control group, AR group, and IL-10 intervention group. The AR model was established in the AR group and IL-10 group. The rats in the control group were treated with normal saline; the rats in the AR group were given 20 μL of saline containing 50 μg of ovalbumin (OVA) every day. The rats in the IL-10 intervention group were intraperitoneally injected with 1 mL of 40 pg/kg IL-10 and provided with OVA. The IL-10 intervention group was composed of mice with AR that received IL-10. The behavior of nasal allergic symptoms (such as nasal itching, sneezing, and runny nose) and the hematoxylin and eosin staining of nasal mucosa were observed. The levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum were determined by enzyme-linked immunosorbent assay. The levels of Treg and Th17 cells in serum were detected by flow cytometry. The protein levels of TGF-β, IL-10, and IL-17 in nasal mucosa were detected by the Western-blot method. The scores of snots, nasal itching, and sneezing in the AR group were significantly higher than those in the control group, while the scores of the above symptoms in the IL-10 intervention group were lower than those in the AR group. The levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum and the protein levels of IL-10 and IL-17 in the nasal mucosa in the AR group were higher than those in the blank control group. Meanwhile, the levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum and IL-10 and IL-17 protein in the nasal mucosa in the IL-10 group were lower than those in the AR group. IL-10 can relieve the allergy of AR rats by affecting the expression of FIB, PCT, and hs-CRP, as well as the balance of the Th17/Treg-IL10/IL-17 axis in the nasal mucosa of AR rats.

Relationship between serum allergen-specific immunoglobulin E and threshold dose in an oral food challenge.

Several studies have reported threshold doses for food allergens. However, evidence regarding potential risk factors for low threshold doses is limited. Moreover, the relationship between threshold dose and specific immunoglobulin E (sIgE) levels to causative foods remains unclear. This study examined the relationship and the risk factors for a low threshold dose. We recruited children with food allergies and examined the risk factors for a positive oral food challenge (OFC) with a low threshold dose and anaphylaxis. We evaluated 2501 children with food allergies (1667 [67%] boys; median age, 4.9 years) to eggs (n= 1096), milk (n= 671), wheat (n= 370), peanuts (n= 258), walnuts (n= 65), and cashews (n= 41). Of these patients, 234 (9%) reacted to ≤30 mg protein of causative foods and 620 (25%) reacted to ≤100 mg protein of causative foods. The sIgE level to causative foods was a significant independent factor for positive OFCs with a threshold dose of ≤30 mg for milk, wheat, and peanuts; ≤ 100 mg for eggs, milk, wheat, peanuts, and cashews; and anaphylaxis from eggs, milk, wheat, peanuts, and walnuts. High sIgE levels to causative foods were associated with a lower threshold dose of the OFC and anaphylaxis during the OFC. Approximately 9% of patients reacted to ≤30 mg protein of causative foods. The potential risks of anaphylaxis should be considered during OFCs for patients with elevated sIgE levels.

The relationship of D. pteronyssinus allergic component sIgE and sIgG4 in house dust mite allergic rhinitis or/and allergic asthma patients

Objective: House-dust mite sensitization is an important cause of allergic asthma and/or rhinitis in southern China. This study aimed to analyze the immune effect and relationship between the Dermatophagoides pteronyssinus components specific immunoglobulin E (sIgE) and sIgG₄. Methods: The serum levels of sIgE and sIgG₄ to D. pteronyssinus allergen components Der p 1, 2, 3, 5, 7, 10, and 23 were detected in 112 patients with allergic rhinitis (AR) and/or allergic asthma (AA). Results: Overall, Der p 1 had the highest positive rate of sIgE (72.3%), followed by Der p 2 (65.2%) and Der p 23 (46.4%). Meanwhile, the highest positive rates of sIgG₄ were for Der p 2 (47.3%), Der p 1 (33.0%), and Der p 23 (25.0%). The patients with AR and AA had a higher positive rate (43.4%) of sIgG₄ than that in the patients with AR (42.4%) and the patients with AA (20.4%; p = 0.043). In patients with AR, the positive rate of sIgE in Der p 1 (84.8%) was higher than that in sIgG₄ (42.4%; p = 0.037), but the positive rate of sIgG₄ in Der p 10 (21.2%) was higher than that in sIgE (18.2%; p < 0.001). Most of the patients were positive for sIgE and sIgG₄ of Der p 2 and Der p 10 at the same time. However, positive results for sIgE alone were just found in Der p 7 and Der p 21. Optimal scale analysis showed that Der p 2, Der p 7, and Der p 21 sIgG₄ were closely related to AR and AA (Cronbach α = 0.917). Conclusion: Herein, the D. pteronyssinus allergen components showed different characteristics among the patients with AR, patients with AA, and patients with AR and AA in southern China. Thus, sIgG₄ may be play an important role in allergic reactions.

Multiplex Specific IgE Profiling in Neonatal Stool of Preterms Predicts IgE-Mediated Disease

Background: The natural history of immunoglobulin (Ig) E-mediated diseases in preterm infants is still elusive. We aimed at developing a non-invasive tool for detecting specific IgE (sIgE) and eosinophil-derived neurotoxin (EDN) in neonatal fecal samples and evaluating its predictive value for the development of IgE-mediated diseases during the first year of life. Methods: We developed a stool extraction protocol, followed by freeze-drying and solubilization. The sIgEs were investigated in neonatal fecal samples from 21 preterm infants with a 300-allergen multiplex and confirmed by a capillary Western blot with a nano-immunoassay. EDN concentration was used to investigate the local eosinophilic component. Results: The multiplexed allergen assay detected sIgE in all of the samples. A Western blot was used to confirm the results. The frequency and levels of sIgE in the neonatal fecal samples differed between the infants who developed IgE-mediated diseases and the controls. Allergen specificity was associated with the development of cow’s milk allergy (CMA) and asthma. The development of CMA was predicted by the sIgE response to milk proteins (sensitivity was 88%; specificity was 78%). The EDN levels predicted the development of IgE-mediated diseases (sensitivity was 100%; specificity was 75%). Conclusion: The non-invasive investigation of neonatal fecal sIgE is a promising tool for predicting the subsequent development of IgE-mediated diseases. Clinical Implications: The non-invasive sIgE and EDN profiling of neonatal fecal samples from preterm infants can predict the development of IgE-mediated diseases.

Allergic March in Children: The Significance of Precision Allergy Molecular Diagnosis (PAMD@) in Predicting Atopy Development and Planning Allergen-Specific Immunotherapy

The allergic march is a progression of naturally occurring symptoms whose nature changes with age. The classic allergic march typically begins in infancy and manifests in the form of atopic dermatitis and food allergy. As immune tolerance develops over time, these conditions may resolve by the age of 3-5 years; however, they may evolve into allergic rhinitis and bronchial asthma. Traditional diagnostic assessments, such as skin prick testing or serum allergen-specific immunoglobulin E (sIgE) level testing, are conducted to introduce effective treatment. Recent years saw the emergence of precision allergy molecular diagnosis (PAMD@), which assesses sIgE against allergenic molecules. This new technology helps more accurately evaluate the patient's allergy profile, which helps create more precise dietary specifications and personalize allergen-specific immunotherapy. This review presents possible predictions regarding the allergic march and the means of controlling it based on PAMD@ results.

Single sIgE for Dermatophagoides pteronyssinus (Dp) is a good screening tool for atopic sensitisation

Background: Limited publications evaluated the Phadiatop application for aeroallergen screen in allergic respiratory diseases (ARD) in Chinese. Our retrospective cohort studied the Phadiatop versus total IgE use in aeroallergen workups, and local aeroallergen sensitisation profiles by reviewing aeroallergen sIgE. We aimed to derive a cost-effective algorithm for ARD workup. Methods: The Phadiatop tests from 694 patients with ARD in 2010–2019 were retrospectively identified. Other associated workups including total IgE, and/or allergen specific sIgE (sIgE), if available, were retrieved and analysed. Besides, a further review was performed on 53 consecutive samples collected during January 2021, for aeroallergen screening. Cost effectiveness of the existing protocol (Phadiatop screening followed by individual aeroallergen characterisation) was compared with a new testing algorithm, which started with dust mite (Dermatophagoides pteronyssinus, Dp) allergy detection. Results: Positivity of Phadiatop and total IgE were 67.3% (n=694) and 66.7% (n=366), with overall agreement being 73.5% (269/366). 34.9% to 45.6% of asthmatic patients had elevated total IgE than Phadiatop. Dp was the most prevalent aeroallergen (> 90%), and its sIgE level correlated best with the Phadiatop sIgE level (R=0.99, p < 0.001). Conclusions: Screening by Dp sIgE is as sensitive as Phadiatop in aeroallergen screen but of lower running cost. It should be the approach in our locality. Reference 1. Vidal C, Boquete O, Fernández-Merino MC, et al. Evaluation of the phadiatop test in the diagnosis of allergic sensitization in a general adult population. J Investig Allergol Clin Immunol 2005; 15: 124–130. 2. Zeng G, Haisheng H, Zheng P, et al. The practical benefit of Phadiatop test as the first-line in vitro allergen-specific immunoglobulin E (sIgE) screening of aeroallergens among Chinese asthmatics: a validation study. Ann Translational Med 2018; 6: 151. 3. Sterner T, Uldahl A, Svensson A, et al. IgE sensitization in a cohort of adolescents in southern Sweden and its relation to allergic symptoms. Clin Molec Allergy 2019; 17: 6.

Molecular allergy diagnostics in predicting oral cow's milk challenge outcome in Finnish children.

Oral food challenges (OFC) are required to diagnose food allergies but are resource-intensive. To reduce the need for OFCs, we sought to determine serum specific immunoglobulin E (sIgE) cutoff levels for cow's milk and its major allergens predicting oral milk challenge outcomes in children with suspected cow's milk allergy. A total of 135 Finnish children (median age, 1.8 years [range, 1.0-14.1 years]) with suspected cow's milk allergyunderwent open OFC with unheated cow's milk. The sIgE levels to milk (f2), casein (Bos d 8), alpha-lactalbumin (Bos d 4),beta-lactoglobulin (Bos d 5), and bovine serum albumin (BSA) (Bos d 6) were measured and compared with the challenge outcomes. Of the 135 OFCs, 5 were excluded from the study due to purely subjective symptoms. Of the 130 remaining OFCs, 98 results (75%) were positive. In a receiver operating characteristic analysis with 1-2-year-old children, no individual allergen sIgE had a better area under the curve than milk sIgE (0.824). A milk sIgE level > 6.30 kU/L gave 94% specificity and 33% sensitivity for positive OFCs. In 3-14-year-old children, a cutoff value >13.9 kU/L predicted a positive OFC result with 93% specificity and 25% sensitivity. Children with moderate-to-severe reactions had higher sIgE levels to milk, alphalactalbumin, and BSA than did children with mild reactions. Molecular allergy diagnostics did not improve the predictive performance compared with milk sIgE. The milk sIgE value that exceeds the cutoff for 95% specificity in combination with the clinical history may help to reduce the need for OFCs. The severity of an allergic reaction cannot reliably be predicted from sIgE measurements.

A new trend in sensitization to cockroach allergen: A cross-sectional study of indoor allergens and food allergens in the inland region of Southwest China.

Despite the increasing prevalence of allergic disease, large-scale studies to investigate allergen sensitization have rarely been conducted in the inland region of Southwest China. This study aimed to investigate the trend of allergen sensitization in mainland China from 2016 to 2017. During the 2-year study period, from 2016 to 2017, the serum samples of 7,759 allergic patients collected from 38 hospitals in Yunnan were detected the specific immunoglobulin E (sIgE) against 8 indoor and food allergens, namely, house dust mite, cockroach, dog dander, mold mix, egg white, milk, crab, and shrimp. The polysensitization patterns were analyzed through cluster analysis, and the relationship between cockroach and other indoor and food allergens was analyzed. Allergen sIgE positivity was prevalent in 45.6% of the population. Cockroach was the most common allergen (27.0%), followed by house dust mite (25.6%), shrimp (18.8%) and crab (15.6%). Three polysensitization clusters were identified: cluster 1): egg white/milk; cluster 2): crab/shrimp/cockroach/house dust mite/dog dander; and cluster 3): mold mix. The sIgE levels and sensitization rates to house dust mite, crab, and shrimp increased with the level of cockroach sIgE (P < 0.05). Based on big data in the real world, we found that there is a new trend in common allergens in Southwest China, where house dust mite is the only available reagent of specific immunotherapy. Cockroaches may become another major allergen in mainland China in the future, and clinicians should be aware of this.

Comparison of perennial and preseasonal allergoid immunotherapy in grass pollen allergic patients.

The clinical and immunological efficacy of preseasonal allergoid immunotherapy has been previously investigated, however, studies comparing the effectiveness of the two protocols are limited in the literature. The aim of this study is to compare the clinical and immunological efficacy of pre-seasonal and perennial allergoid immunotherapy. This is a prospective cross sectional two-arm study. During the season; symptom and medication scores were filled. Before and at the end of the season; RQLQ was applied, Phl p sIgE, sIgG4 and IL-10 levels were measured. In preseasonal group patients had better symptom control for most of the weeks, particularly during the peak pollen period (April: w-2 & w-4, p = 0.04; May: w-2, p = 0.02; June: w-1, w-2, p = 0.02; w-3, w-5, p = 0.03; July: w-2, p = 0.01; w-3, p = 0.02; w-4, p = 0.04). In the perennial group, sIgG4 [1st time point: preseasonal 0.02 mgA/L vs perennial 0.13 mgA/L (p < 0.0001); 2nd time point: preseasonal 0.52 mgA/L vs perennial 0.33 mgA/L; 3rd time point: preseasonal 0.04 mgA/L vs perennial 0.12 mgA/L (p < 0.0001)] and IL-10 (1st time point: preseasonal 1.45 pg/ml vs perennial 2.03 pg/ml; 2nd time point: preseasonal 2.29 pg/ml vs perennial 2.19 pg/ml; 3rd time point: preseasonal 2.32 pg/ml vs perennial 2.16 pg/ml) levels were higher and more stable. Preseasonal immunotherapy provided better control of symptoms throughout the pollen season. However, the blocking antibody response was stronger and more permanent in the perennial immunotherapy group.

Причинно-значимые аллергены и спектр сенсибилизации детей, перенесших пищевую анафилаксию

Aim: to assess the spectrum of sensitization and reveal causative allergens in Ekaterinburg children with the clinical history of food-induced anaphylaxis (FIA) for reducing the number of life-threatening food allergy (FA) episodes in these children. Patients and Methods: the study included 60 children — 36 (60.0%) boys and 24 (40.0%) girls aged from 4 months to 16 years who lived in Yekaterinburg. All children had (FIA) episodes in their clinical histories. The children underwent physical examination, and their allergy- focused clinical history was taken. Also, the ISAC-112 ImmunoCAP assay, a multiplex test with allergen components, was used. Results: the sensitization was assessed, and the causative allergens were identified in 100% of cases. In 31 children (51.67%) FIA was initiated by milk proteins (Bos d4, Bos d5, Bos d8); in 10 (16.67%) – chicken egg (Gal d2, Gal d1); in 10 (16.67%) – walnut (Jug r1, Jug r2, Jug r3); in 9 (15.00%) – fish (Gad c1); in 7 (11.67%) – kiwi (Act d1); in 7 (11.67%) – peanut (Ara h1, Ara h2, Ara h3, Ara h6); and in 20 (33%) – by different nuts (Ber e1, Ana o2, Cora 9, Cora 8). Elevated specific immunoglobulin E (sIgE) levels for birch tree allergens (Bet v1) were found in 39 (65.00%) patients, cat allergens (Fel d1, Fel d2, Fel d4) – in 41 (68.33%), dog allergens (Can f1, Can f2, Can f3, Can f5) – in 24 (40.0%), timothy allergens (Phl p1, Phl p4, Phl p5) – in 10 (16.6%), artemisia allergens (Art v1) – in 8 (13.3%), and house dust mites in 2 (3.33%). Respiratory symptoms in sensitized children with FIA developed in 4 of 5 cases. Conclusion: to reduce the number of life-threatening FA episodes in children with FIA it is necessary to reveal and assess the entire spectrum of sensitization, identify the causative allergens and triggers of potential anaphylactic reaction for the further development of an elimination diet and individualized patient management plan. KEYWORDS: food allergy, food-induced anaphylaxis, children, allergens, sensitization. FOR CITATION: Lepeshkova T.S. Causative allergens and sensitization spectrum in children with the history of food-induced anaphylaxis. Russian Medical Inquiry. 2023;7(2):75–80 (in Russ.). DOI: 10.32364/2587-6821-2023-7-2-75-80.

Safety of House Dust Mite Subcutaneous Immunotherapy with a rush and cluster combination protocol in the build-up phase.

Conventional and cluster subcutaneous immunotherapy (SCIT) are effective but may be time-consuming. Rush SCIT may offer a more convenient treatment option to patients and be of shorter duration; however, it is also associated with a higher incidence of systemic adverse reactions. Therefore, a combination of protocols between rush and cluster SCIT could have a superior risk-benefit ratio. To determine the safety of the combination of rush and cluster HDM-SCIT and to identify the risk factors for local and systemic adverse reactions. We retrospectively reviewed the charts of patients who received HDM-SCIT, with rush and cluster combination protocols, at a tertiary care hospital between January 2009 and December 2020. Data were collected at the initial visit (demographic data; underlying allergic disease; current medication; and laboratory investigation results including skin prick test, serum specific IgE (sIgE) levels to aeroallergen, total IgE, and eosinophil count) and follow-up visits (rate and severity of local and systemic adverse reactions). In total, 698 injections (28 patients) were reviewed. Overall, 13 patients developed systemic adverse reactions, at 3% (21/698) per injection visit. All reactions occurred within 60 minutes. In total, 6 patients experienced large local reactions, at 1.1% (8/698) per injection visit. A high level of sIgE to D. pteronyssinus was significantly associated with systemic adverse reactions (HR = 1.02; P = 0.009). HDM-SCIT with a combination of rush and cluster schedules in the build-up phase could be used as an alternative protocol, given its acceptable systemic adverse reaction rate and shortened duration.

Specific immunoglobulin G4 correlates with Th2 cytokine reduction in patients with allergic asthma treated by Dermatophagoides pteronyssinus subcutaneous immunotherapy

BackgroundThe modulations of lymphocyte subsets and cytokine production due to subcutaneous allergen immunotherapy (SCIT) are not fully clarified. ObjectiveWe investigated the changes in T-lymphocyte subsets and serum Dermatophagoides pteronyssinus-specific immunoglobulin G4 (Der-p sIgG4), as well as cytokine production during Der-p SCIT, in patients with allergic asthma. MethodsThis study involved 20 patients with allergic asthma who were receiving 156-week Der-p SCIT and 20 patients without SCIT (non-SCIT). We measured symptom and medication scores (SMS), serum Der-p sIgG4 levels, CD4+CD25+Foxp3+ T regulatory (Treg), CD4+IL-4−IFN-γ+ T-helper (Th) 1, and CD4+IL-4+IFN-γ− Th2 lymphocyte percentages in peripheral blood mononuclear cells (PBMCs) with/without Der-p extract stimulation at weeks 0, 4, 12, 16, 52, 104, and 156. Cytokine release inhibition assays were performed by incubation with serum from SCIT and non-SCIT patients, Der-p allergen, and PBMCs. Levels of interleukin (IL)-4, IL-5, IL-10, IL-13, IL-17, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1 were evaluated in supernatant. ResultsWe found that SCIT patients had significantly lower SMS after week 52. Der-p sIgG4 levels in SCIT patients significantly increased at week 16 compared with non-SCIT subjects. CD4+IL-4+IFN-γ− Th2% in SCIT patients showed a significant decrease from weeks 104–156 compared with week 0, while no change was observed in CD4+CD25+Foxp3+ Treg and CD4+IL-4−IFN-γ+ Th1 percentages. IL-5, IL-13, IL-4, IL-17, and TNF-α levels in supernatant of PBMCs cultured with serum of SCIT patients after 16 weeks showed significant lower levels compared with non-SCIT patients, and showed significant reverse associations with Der-p sIgG4 levels. ConclusionSCIT induced Dep-p sIgG4 may be involved in downregulating Th2 cytokine production in Der-p allergic asthma patients.

Skin prick test and serum specific IgE in predicting dust mite-induced allergic rhinitis diagnosed from nasal provocation test in chronic rhinitis children.

Allergen skin prick test (SPT) and serum specific immunoglobulin E (sIgE) are effective diagnostic tests in allergic rhinitis (AR), however, positive results may not always correlate with clinical allergies. A nasal provocation test (NPT) can identify the causative allergen for immunotherapy, but it's not routinely performed. To establish the cutoff value for the house dust mite (HDM) SPT mean wheal diameter (MWD) and HDM sIgE level for identifying children with HDM-induced AR diagnosed from NPT. Children aged 5 to 18 years old with chronic rhinitis were evaluated by HDM SPT, sIgE, and NPT. Children with positive NPT results indicated HDM-induced AR. The cutoff values of the HDM SPT and sIgE level for predicting positive NPT were determined using a receiver operating characteristic curve. A total of 245 children with a mean age of 9.53 ± 3 years were enrolled. HDM SPT results were positive (≥ 3 mm) in 160 (65.3%) children. HDM NPT results were positive in 176 (71.8%) children. Among children with positive HDM SPT (n = 160), 153 children (95.6%) were confirmed as having AR on NPT findings. The cutoff values for positive NPT responses were 6.6 mm for HDM SPT (yielding 100% specificity and 100% positive predictive value) and 17.0 kUA/L for sIgE (98.6% specificity and 99.2% positive predictive value). This study proposes HDM SPT and sIgE cutoff values for use in the diagnosis of HDM-induced AR based on NPT. These cutoff values can be used to identify HDM-induced AR children who might benefit from immunotherapy.

The influence of &lt;i&gt;Aspergillus fumigatus&lt;/i&gt; micromycetes on immune response regulation in patients with asthma

Introduction. Aspergillus fumigatus is able not only to sensitize patients with atopy, but also to colonize the respiratory tract, remaining a constant source of allergens due to the small spore size and thermal tolerance. Currently, the role of micromycetes in the immunopathogenesis of asthma has been poorly studied. The objective was to evaluate the features of the immune response regulation in patients with allergic bronchopulmonary aspergillosis (ABPA) or asthma with sensitization to A. fumigatus. Materials and methods. There were enrolled 15 patients with ABPA, 10 patients with asthma with sensitization to A. fumigatus, 16 patients with asthma without sensitization to A. fumigatus. The control group consisted of 16 apparently healthy volunteers. All patients underwent a clinical and functional examination. The subpopulations of blood lymphocytes were assessed by flow cytometry. The A. fumigatus allergen was added to peripheral blood samples to evaluate the production of IFN, IL-10 and IL-13. The serum cytokine levels in cell culture supernatants, as well as total IgE, A. fumigatus-specific IgE (sIgE) as well as thymus and activation-regulated chemokine (TARC) level were measured by enzyme-linked immunosorbent assay. Results. Significantly higher serum levels of total IgE, A. fumigatus-specific sIgE and TARC were found in patients with ABPA and asthma with sensitization to A. fumigatus compared to patients with asthma without sensitization to A. fumigatus. The results of lymphocyte immunophenotyping revealed significant excess of memory Th2 cells and T-regulatory cells in all patients with asthma compared to the control group. The count of Tfh2 was higher but memory Th17.1 cells were lower in patients with sensitization to A. fumigatus compared to those of apparently healthy volunteers. Patients with ABPA had significantly higher count of memory Th2 cells and TARC level compared to patients with asthma sensitized to A. fumigatus. The increased activity of memory Th2 cells is confirmed by increased secretion of IL-13 and IL-10 following along with decreased IFN production in response to specific fungal allergen stimulation of blood cells compared to the patients with asthma and the control group. A positive correlation was revealed between the count of memory Th2 cells and the levels of sIgE, IgE, TARC, a negative correlation with FEV1. Conclusion. Thus, exposure to A. fumigatus significantly enhances the activity of memory Th2 cells in patients with asthma which can lead to severe disease course and development of allergic bronchopulmonary aspergillosis. The features of the immune response identified dictate a need for a personalized approach to choose therapeutic tactics in such patients.

Identification of allergens in coconut milk and oil with patients sensitized to coconut milk in Sri Lanka

BackgroundDespite the low prevalence of IgE sensitivity to fresh or boiled coconut milk and coconut oil, those may contain allergens of which the clinical significance remains undetermined. This study aimed to identify and compare allergens in fresh coconut milk (FCM), boiled coconut milk (BCM), unrefined wet-processed coconut oil (WPCO), and dry-processed coconut oil (DPCO) using sera from patients with allergy to coconut milk.MethodsThe study included 18 patients with immediate hypersensitivity to coconut milk, including five who developed anaphylaxis. Sensitization was assessed by skin prick test and ImmunoCAPs using commercially available coconut extracts. Immunoblotting was performed to identify and compare allergen profiles.ResultsTotal sIgE levels and overall IgE reactivity of patients with anaphylaxis were higher compared to patients with allergy. Twelve allergens ranging from 5 to 128 kDa including six novel allergens with 5, 12, 47, 87, 110, and 128 kDa were visualized in immunoblots with FCM. Similarly, nine allergens of 5, 12, 17, 32, 35, 47, 87, 110, and 128 kDa were detected in BCM. One allergen (110 kDa) was discerned in all four extracts. Higher IgE prevalence was detected with three allergens of 55, 87, and 110 kDa.ConclusionsAllergens of BCM and unrefined coconut oil (WPCO and DPCO) were determined for the first time. Novel allergens of 87 and 110 kDa and the 55 kDa allergen have the highest potential to be used in Component Resolved Diagnostics. Further, these findings demonstrate that, patients who have an allergy to coconut milk could also react to boiled coconut milk and unrefined coconut oil.

The quantity of unheated milk tolerated as a predictor of tolerance to baked milk.

Tolerance of baked milk indicates a good prognosis in IgE-mediated cow's milk allergy. The present study aims to investigate the predictors of baked milk tolerance, particularly the amount of milk tolerated in the first oral food challenge (OFC) test, in children with IgE-mediated cow's milk allergy. The study included 35 cases who were diagnosed with IgE-mediated cow's milk allergy upon open OFC testing in the Pediatric Allergy Clinic. Four weeks after the diagnosis, skin prick test (SPT) and OFC were performed with baked milk. Cases who did and did not develop reactions during OFC with baked milk were compared regarding clinical and laboratory parameters. Twelve cases (33.3%) did not develop a reaction during OFC with baked milk. Those who had low levels of casein sIgE, β-lactoglobulin sIgE, and β-lactoalbumin sIgE; small SPT wheal diameter for baked milk and β-lactoalbumin; and a large amount of unheated milk tolerated in the first OFC were found to be tolerant to baked milk (p < 0.05). For predicting baked milk tolerance, a cut-off level of the amount of unheated milk tolerated in OFC was calculated as 620 mg [with the area under the curve (AUC) 0.88 (95% confidence interval 0.77-0.99) in ROC curve analysis]. If a child with cow's milk allergy is able to tolerate more than 620 mg of milk protein during challenge with unheated milk, this may show that this child will tolerate baked milk, meaning that the child will be able to tolerate cow's milk in the future.

Increasing Severity of Early-onset Atopic Dermatitis, but Not Late-onset, Associates With Development of Aeroallergen Sensitization and Allergic Rhinitis in Childhood

To investigate if there is an association between severity and time of onset of atopic dermatitis and the later development of aeroallergen sensitization or allergic rhinitis.The study included 368 children from the Copenhagan Prospective Studies on Asthma in Childhood (COPSAC) at-risk mother-child cohort. Inclusion criteria included children born between August 1998 and December 2001 to mothers with a history of asthma. The study population was followed from birth until 12 years of age.The study was a single-center, prospective trial. Study participants had planned clinic visits, arranged acute care visits for allergy-related flare ups, and were examined by a COPSAC research physician with dermatology training. Atopic dermatitis was diagnosed according to Hanifin and Rajka criteria and severity was scored using the SCORAD index. Aeroallergen sensitization assessment was conducted via specific-IgE (sIgE) levels at age 6 and 12 years, and sensitization was defined as ≥0.35 kUA/L. Allergic rhinitis assessment at age 7 and 12 years was conducted via parental interview on history of symptoms and congruence with allergy testing (positive sIgE or skin prick test).At 6 years of age, aeroallergen sensitization was noted in 29 of 84 (35%) children with early onset atopic dermatitis versus 45 of 207 (22%) children without. At 12 years of age, aeroallergen sensitization was noted in 48 of 89 (54%) children with early onset atopic dermatitis versus 92 of 215 (43%) children without. Among children with early onset atopic dermatitis and aeroallergen sensitization, a 1 point increase in SCORAD had an odds ratio (OR) = 1.08 (1.03–1.14), P < .01 at 6 years and OR = 1.08 (1.03–1.14), P < .01 at 12 years. In contrast, in children with late onset atopic dermatitis, SCORAD had no significant association with aeroallergen sensitization. In children with early onset atopic dermatitis, allergic rhinitis was noted in 17 of 83 (20%) children at 7 years of age, whereas at 12 years of age it was noted in 38 of 98 (38%) children. The same could be seen with severity of SCORAD and association with development of allergic rhinitis. Additionally, these observations had a stronger association in children with filaggrin mutation. Adjusting for sex, older siblings, parental allergic rhinitis, breastfeeding, and smoking did not significantly alter results.More severe early onset atopic dermatitis was found to be associated with aeroallergen sensitization and allergic rhinitis.Atopic dermatitis is a very common childhood disorder and this study demonstrates that earlier and better control of atopic dermatitis may prevent the development of allergic rhinitis. This suggests that an infant’s skin barrier may be more permeable to aeroallergen penetration and/or that early onset versus late onset atopic dermatitis represent different endotypes. This study emphasizes the need for eczema control in atopic infants.URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1111/all.15108