Mechanisms for initiation of food allergy by skin pre-disposed to atopic dermatitis.

Food allergy can be life-threatening and often develops early in life. In infants and children, loss-of-function mutations in skin barrier genes associate with food allergy. In a mouse model with skin barrier mutations (Flakey Tail, FT+/- mice), topical epicutaneous sensitization to a food allergen peanut extract (PNE), an environmental allergen Alternaria alternata (Alt) and a detergent induce food allergy and then an oral PNE-challenge induces anaphylaxis. Exposures to these allergens and detergents can occur for infants and children in a household setting. From the clinical and preclinical studies of neonates and children with skin barrier mutations, early oral exposure to allergenic foods before skin sensitization may induce tolerance to food allergens and thus protect against development of food allergy. In the FT+/- mice, oral food allergen prior to skin sensitization induce tolerance to food allergens. However, when the skin of FT+/- pups are exposed to a ubiquitous environmental allergen at the time of oral consumption of food allergens, this blocks the induction of tolerance to the food allergen and the mice can then be skin sensitized with the food allergen. The development of food allergy in neonatal FT+/- mice is mediated by altered skin responses to allergens with increases in skin expression of interleukin 33, oncostatin M and amphiregulin. The development of neonate food allergy is enhanced when born to an allergic mother, but it is inhibited by maternal supplementation with α-tocopherol. Moreover, preclinical studies suggest that food allergen skin sensitization can occur before manifestation of clinical features of atopic dermatitis. Thus, these parameters may impact design of clinical studies for food allergy, when stratifying individuals by loss of skin barrier function or maternal atopy before offspring development of atopic dermatitis.

Identifying Region-Specific Allergy Sensitization Clusters to Optimize Diagnosis and Reduce Costs.

OBJECTIVE: To delineate quantitatively the allergen sensitization patterns in a large pediatric cohort and inform the selection of a region-specific panel of allergen tests for timely and cost-effective in vitro atopy screening. STUDY DESIGN: IgE levels for specific allergens from patients in the Texas Children's Health System were analyzed retrospectively. Statistical and network analyses were conducted to reveal sensitization patterns. RESULTS: Network analysis of 114 distinct allergens among 12 065 patients identified 2 main groups of allergens: environmental and food. Approximately 67.5% of patients were sensitized to environmental allergens, 47.2% to food allergens, and 7.3% to at least 1 allergen from both groups. We identified a novel panel of 13 allergens that could detect sensitization in 95% of patients, whereas panels of 7 allergens within each category effectively identified sensitization in 95% of patients with specific sensitivities. This data-driven approach is estimated to reduce overall testing costs by 52%. In agreement with literature, we observed correlations among allergens within specific categories, such as pollen, shellfish, nuts, and dairy allergens. CONCLUSIONS: This study provides insights into allergen sensitization patterns informing an algorithmic testing approach tailored for primary care settings. The use of a region and population-specific test panel can efficiently identify atopy, leading to more targeted testing. This strategy has the potential to refine laboratory testing, reduce costs, and improve the appropriateness of referrals to allergy specialists, ultimately enhancing diagnostic accuracy and resource allocation.

Indoor Environmental Exposures and Their Relationship to Allergic Diseases.

Cockroach, dust mite, cat, dog, mouse, and molds are major indoor allergens that have been associated with the development of allergic diseases and disease morbidity in allergen-sensitized individuals. Physical characteristics, such as allergen particle size, hydrophobicity, and charge, can determine an allergen's propensity to become airborne, location of respiratory tract penetration, and ability to elicit IgE responses in genetically predisposed individuals. Standardization and recent advancements in indoor allergen assessment serve to identify sources and distribution of allergens in a patient's home and public environment, inform public policy, and monitor the efficacy of allergen avoidance and therapeutics. Allergen exposure interventions have yielded mixed results with current US and international asthma guidelines differing on recommendations. A pragmatic, patient-centered approach to allergen avoidance includes: (1) tailoring intervention to the patient's sensitization and exposure status, (2) using a rigorous multifaceted intervention strategy to reduce allergen exposure as much as possible, and (3) beginning the intervention as soon as the patient is diagnosed. Further research into the risks/benefits of early allergen exposure, rapid and affordable in-home allergen assessment, and best practices for environmental control measures for asthma is needed.

Comorbidity of ADHD and allergic diseases in early adolescence: The role of parental smoking at home.

A growing body of research suggests an association between attention deficit hyperactivity disorder (ADHD) and allergic disorders, but little work has been done to explore the role of external factors such as parental smoking at home in the development of comorbid ADHD and allergic disorders. This study aimed to examine the association between allergic diseases and ADHD adjusted for exposure to parental smoking at home in early adolescents. We recruited 250 male (41.7%) and 350 female (58.3%) adolescents (mean [SD] age, 13.29 [0.52] years) via chain-referral sampling. Their ADHD symptoms were assessed by the parent proxy-report version of the Chinese Strengths and Weaknesses of Attention-Deficit/Hyperactivity-symptoms and Normal-behaviours (SWAN) rating scale. Data on the participants' history of clinician-diagnosed allergic diseases, family socio-demographics, and parental smoking habit were collected using a parent-completed questionnaire. Regression analyses were performed to examine the associations of interest. The levels of ADHD symptoms were comparable between allergic and non-allergic participants after controlling for child and family demographics and parental smoking at home. Notably, the risk of probable ADHD was particularly high in participants with food allergies (odd ratio = 4.51, p = 0.011) but not in those with allergic rhinitis after adjusting for parental smoking at home. Our findings suggest that second-hand smoke exposure at home is a potential risk factor underlying the link between ADHD and allergic diseases. Current management guidelines should emphasize the importance of early identification and cessation of tobacco smoke exposure for prevention of comorbidity of ADHD and allergic disorders. Clinical Trial Registration (if any): NA.

Suppression function against environmental dust exposure after Dermatophagoides pteronyssinus immunotherapy is associated with production of specific and cross-reactive immunoglobulin G4.

BACKGROUND: Whether Dermatophagoides pteronyssinus (Der-p) allergen immunotherapy (AIT) can induce Dermatophagoides farina (Der-f)-specific immunoglobulin (sIg) G4 production, and tolerance to environmental allergens has not been fully investigated. OBJECTIVE: We aimed to determine serum Der-p-sIgG4 and Der-f-sIgG4 levels in asthma and/or rhinitis patients undergoing Der-p AIT and their ability to reduce immune responses triggered by indoor dust extracts. METHODS: We performed a real-world prospective trial and enrolled patients with allergic rhinitis and/or asthma in Guangzhou, China. These patients received either Der-p AIT (SCIT group) or routine medications (non-SCIT group) for 156 weeks. Clinical outcomes were assessed by the combined symptom medication score (SMS) and FEV1 % changes. House dust samples were collected to analyse allergen levels. Serum levels of Der-p-sIgG4 and Der-f-sIgG4, serum inhibitory capacity against Der-p, Der-f and indoor dust extract by sIgE-facilitated allergen binding to B cells (IgE-FAB), and serum blocking indoor dust extract-induced basophil activation inhibition assays (BATI) in peripheral blood monocytes were carried out at weeks 0, 4, 12, 16, 52, 104 and 156 after the initiations of the treatments. RESULTS: Our study enrolled a total of 60 participants, with 30 patients in each group. Patients in the SCIT group had significantly improved SMS when compared with the baseline and the patients in the non-SCIT group. Median levels of Der-p 1 and Der-f 1 in indoor dust extract were 1.86 µg/g and 4.74 µg/g, respectively. Serum Der-p-sIgG4 and Der-f-IgG4 levels in SCIT patients showed a significant increase from weeks 12 to 156. Serum in these SCIT patients could significantly block Der-p, Der-f and indoor dust extract formation of allergen-sIgE complex and reduced the threshold of IgE-FAB from 16 weeks after the initiation of the treatment. The capacity to inhibit Der-p, Der-f and indoor dust extract BATI was observed in SCIT serum after 12 weeks. Der-p-sIgG4 and Der-f-sIgG4 had a significant correlation with IgE-FAB and BATI in SCIT patients at all time points. CONCLUSION: Single Der-p immunotherapy induced both Der-p-sIgG4 and Der-f-sIgG4 production, which might cross-reactively induce tolerance against environmental allergen exposure in patients with asthma and/or rhinitis.

Regional differences in the prevalence of sensitization to environmental allergens: Analysis on IgE antibody testing conducted at major clinical testing laboratories throughout Japan from 2002 to 2011.

BACKGROUND: Identification of sensitized allergens for patients with respiratory allergy is an important step in disease care and environmental allergen control. The Japanese archipelago belongs to various climate categories due to its length from north to south which transverse the subarctic in the north to the subtropical in the south, suggesting substantial regional differences in dominant environmental allergens. However, few studies have assessed the regional differences in the prevalence of sensitization to environmental allergens. METHODS: We requested three major clinical testing laboratories to provide us with summarized results of antigen-specific IgE-antibody (Ab) measurements. These measurements were collected for clinical purposes throughout Japan from 2002 through 2011. The prevalence of positivity for IgE-Ab against 19 environmental allergens was calculated for each prefecture in order to evaluate regional differences. RESULTS: Test data on specific IgE-Ab of 19,969,753 orders were analyzed. The prevalence of positivity for house dust mites was high and the regional difference was low, whereas apparent regional differences were found for pollen, insects, and fungi. The prevalence of positivity for Japanese cedar was low in Hokkaido and Okinawa, while those to alder was highest in Hokkaido. Higher prevalence for insects was observed in southern areas (Okinawa and prefectures in Kyusyu). CONCLUSIONS: Findings of this study clearly demonstrated regional differences in the prevalence of sensitization to environmental allergens in Japan and the study also provides useful information for the clinician when deciding which allergens should preferentially be measured for IgE-Ab after considering regional difference.

Prominent IgE-binding and cytokine-inducing capacities of a newly cloned N-terminal region of Der f 14, an apolipophorin-like house dust mite allergen.

We previously characterized a 177-kDa allergen, M-177, from Dermatophagoides farinae. Thereafter, a counterpart to M-177 for Euroglyphus maynei was cloned as Eur m 14, and its sequence revealed that two environmental allergens, Mag 1 and Mag 3, are digested fragments of M-177. The aims of this study were to clone the cDNA of Der f 14 corresponding to M-177 and to elucidate the allergenic capacities of the N-terminal fragment of Der f 14 (Der f 14-N). Recombinant allergens were produced as trigger-factor-fused proteins in Escherichia coli. Der f 14-N showed the highest IgE-binding frequency among Der f 14-derived fragments in patients allergic to house dust mite by enzyme-linked immunosorbent assay. Der f 14-N showed the highest capacity to induce cell proliferation in murine lymphocyte and human peripheral mononuclear cells among Der f 14-derived fragments. Der f 14-N induced IL-13, IFN-γ and IL-17 production more than Der f 1 and Der f 2 in mouse, and induced IL-5 and IFN-γ production at levels comparable to those of Der f 1 and Der f 2 in some patients. The high prevalence of IgE binding to the Der f 14-N indicates that it could be an important mite allergen.