Allergic Phenotype Research Articles

COVID-19 Course in Allergic Asthma Patients: A Spanish Cohort Analysis

PurposeThe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a high impact on patients with chronic diseases. In the literature, there are different perspectives on asthma as comorbidity or risk factor on COVID-19 severity.Patients and MethodsThe aim of this retrospective study across 13 allergy departments in Spain was to determine the severity of COVID-19 in asthmatic adults followed in allergy departments and its relationship with atopy, clinical and demographic characteristics, phenotypes and laboratory data. In addition, lung function test and asthma control test (ACT) before and after COVID-19 were analyzed. Data was obtained from electronic medical records from March 2020 to April 2021.ResultsTwo hundred one asthmatic patients were diagnosed with COVID-19 infection by validated detection test. About 30% of the patients were admitted for bilateral pneumonia. Advanced age, elevated D-dimer, lower numbers of lymphocytes and eosinophils, heart diseases and hypertension were associated with severe COVID-19. Allergic and mixed allergic/eosinophilic phenotype and their biomarkers (total IgE, aeroallergens sensitizations, allergic rhinitis, and blood eosinophilia) were related to fewer hospital admissions. Poor control and lower forced expiratory volume in the first second (FEV1) were related to worse prognosis of COVID-19.ConclusionAsthmatic patients with allergic and eosinophilic phenotype have a better evolution of COVID-19 and lower risk of admissions. Older patients, cardiovascular comorbidities, AERD and eosinopenia are related to severity COVID-19.

Features of the Gut Microbiome Relate to Allergic Asthma Phenotypes in Inner-City Children

In young children, processed food consumption relates to the gut microbiome and metabolic dysfunction associated with atopy and asthma. However, whether gut microbes and their products interact with dietary exposures to influence allergy and asthma phenotypes is unknown.

Значення однонуклеотидних поліморфізмів в генах mTOR (rs11121704) та ATG5 (rs510432) в розвитку алергічних захворювань у дітей

Мета цього дослідження — визначення зв’язку однонуклеотидних поліморфізмів в генах mTOR (mammalian target of rapamycin; мішень рапаміцину у ссавців) і ATG5 (autophagy related gene 5; ген автофагії 5) та розвитку алергічного фенотипу у дітей. Генотипування mTOR (rs11121704) та ATG5 (rs510432) проводили в групі хворих з атопічними захворюваннями і контрольній групі за допомогою полімеразної ланцюгової реакції у реальному часі. Виявлено, що у 50 (54,9 %) пацієнтів і 43 (49,4 %) здорових дітей наявна мажорна алель (ТТ) поліморфізму rs11121704; 36 (39,6 %) і 32 (36,8 %) відповідно мали гетерозиготну алель (ТС); у 5 (5,5 %) і 12 (13,8 %) виявлено мінорну алель (СС). Варіанти з генотипом СС rs11121704 у гені mTOR визначалися у 2,5 раза частіше у контрольній групі, ніж серед хворих. Алельні варіанти в гені ATG5 розподілилися так: 51 (52 %) пацієнт та 43 (44,3 %) здорових дитини мали гетерозиготну алель (СТ), 29 (29,6 %) і 21 (21,6 %) відповідно мав мінорну алель (ТТ), у 18 (18,4 %) та 33 (34 %) була мажорна алель (СС). ТТ-генотип асоціюється з підвищеним ризиком ранньої маніфестації бронхіальної астми (до 3 років життя). Вважаємо, що поліморфізми в генах mTOR (rs11121704) та ATG5 (rs510432) можуть служити корисними прогностичними маркерами для оцінки ризику виникнення бронхіальної астми та іншої алергічної патології у дітей.

The Role of Protein Kinase mTOR in Th2 Polarization of the Immune Response in Bronchial Asthma in Сhildren

Objective of this study was to determine whether single-nucleotide polymorphism (SNP) in mTOR gene is associated with development of allergic phenotype in children. Methods. Genotyping for mTOR (rs11121704) was performed in the following populations: patients with asthma (n = 91; ages 5–18 years), and control group (n = 87; ages 5–18 years) using real-time polymerase chain reaction. Results. We have found that 50 (54.9 %) of patients from the study group and 43 (49.4 %) subjects from the control group had major allele of rs11121704 in mTOR, 36 (39.6 %) and 32 (36.8 %), respectively, — heterozygous allele, and 5 (5.5 %) and 12 (13.8 %) — minor allele. Variants of rs11121704 minor genotype in the gene mTOR were 2.5 times more likely in the control group than among patients of the study group. Conclusions. We supposed that SNP in mTOR may independently serve as perspective marker to predict the development of asthma and other allergic diseases among children.

Contribution of the Leukocyte Adherence Inhibition Test to the Evaluation of Cellular Immunoreactivity against Latex Extracts for Non—IgE-Mediated Latex-Fruit-Pollen Syndrome in Allergic Candidates to Exclusion Diets and Allergic Desensitization

Background: Due to the lack of standardized laboratory procedures able to demonstrate specific non—IgE-mediated immune responses against latex allergens, these conditions are diagnosed mostly by clinical criteria based on empiric exclusion prescriptions monitored by in vivo challenge tests.
 Objective: To evaluate the opportunity of an ex vivo challenge immunoassay, the Leukocyte Adherence Inhibition (LAI) Test (LAIT), to discriminate non—IgE-mediated latex-specific immunoreactivity.
 Methods: Ex vivo challenge tests performed with Hevea Brasiliense’s latex extract, monitored by LAIT, were assayed in an asymptomatic control group and a group of patients with diverse respiratory and cutaneous non—IgE-mediated allergic conditions, clinically diagnosed by a certified allergologist.
 Results: The mean LAI of the control group was 8.3%. The mean LAI of the complete patients’ group was 41.1%. The non-parametric Wilcoxon-Mann-Whitney U (WMWU) test comparing the control group with the whole patient’s group showed significance with a p-value < 0.00001. The WMWU test comparing the control group with each other patient’s group showed significance with a p-value < α = 0.05 for all comparisons. The WMWU test comparing the patients’ groups between each other did not show any significant p-value.
 Conclusion: Several patients from the diverse non—IgE-mediated allergic phenotypes presented variable immunoreactivity against the latex extract, as demonstrated by the LAIT, which proved to be an easy, quick, and inexpensive ex vivo immunoassay with the potential to predict individual immunoreactivity against Hevea brasiliensis latex allergens in real-world patients with non—IgE-mediated allergies.

Непредсказуемый сценарий течения аллергических заболеваний респираторной системы у беременных

The article presents the analysis of literature data on the pathogenesis, course and pharmacotherapy in pregnancy during respiratory allergic diseases. The article also considers the systematized ARIA recommendations (Updated 2020) on the diagnosis and pharmacotherapy of allergic rhinitis (AR) in pregnancy, differential diagnosis concerning nasal breathing disorders of atopic and non-atopic etiology during gestation, and the developed therapeutic methods for the patient management (in particular, pregnant women) with an allergic phenotype (a combination of asthma with allergic rhinitis and/or atopic dermatitis). The association between the uncontrolled course of allergic rhinitis in pregnant women and the risk of the bronchial asthma onset has been proven. Of utmost importance, for improving perinatal outcomes is the optimization of therapy and symptom control of allergic diseases during pregnancy in the interdisciplinary practice of an obstetrician-gynecologist and allergist/immunologist. AR in pregnancy should be differentiated from the most common form of nasal breathing disorders in pregnant women — vasomotor rhinitis. Severe uncontrolled vasomotor rhinitis in pregnant women, as an individual nosological form, can worsen the existing AR and bronchial asthma course. The authors present a mathod for the AR step therapy based on pharmacological characteristics and safety profile of drugs in pregnancy. KEYWORDS: allergic rhinitis, bronchial asthma, pregnancy, vasomotor rhinitis of pregnant women, pharmacotherapy, obstetric complications. FOR CITATION: Paschenko A.A., Dobrokhotova Yu.E., Fomina D.S., Pashchenko M.G. Uncontrolled course of respiratory allergic diseases in pregnant women. Russian Journal of Woman and Child Health. 2022;5(2):122–128 (in Russ.). DOI: 10.32364/2618-8430- 2022-5-2-122-128.

A small proline-rich protein (SPRR) gene variant contributes to atopic eczema and eczema-associated asthma susceptibility.

There is some evidence that genetic variants in the epidermal differentiation complex (EDC) genes on chromosome 1q21 may be involved in the pathogenesis of atopic eczema (AE) similar to the well-known filaggrin gene (FLG) mutations. To evaluate the association of SNP in the small proline-rich protein 2B (SPRR2B) gene with atopic eczema and other allergic phenotypes and to investigate its possible interaction with FLG mutations. One hundred and eighty-eight children less than 2 years old were screened for the variant of allele rs6693927 in the SPRR2B gene and for 4 most prevalent FLG mutations. The variant of allele rs6693927 and all FLG mutations were genotyped by real-time polymerase chain reaction assays with subsequent melting curve analysis using SimpleProbe® probes. The allele rs6693927[A] was associated with a significantly increased risk of AE (OR = 3.02; 95% CI: 1.17-8.00; p = 0.011) and the effect was independent of FLG risk alleles. The largest effects were observed in patients with a combined asthma-plus-eczema phenotype (OR = 5.44; 95% CI: 1.17-25.16; p = 0.029). Finally, in eczema, we found interactions of rs6693927[A] with FLG mutations, the risk of eczema was the most increased in the subjects who combined both rs6693927[A] allele and FLG mutations. The SPRR2B risk variant may play an important role in the development of atopic eczema and the particular eczema-associated asthma phenotype in young children. The effect seems to be independent of, and supplementary to, the well-known FLG mutations and may be modulated by gene-gene interactions.

Primary atopic disorders and chronic skin disease.

Primary atopic disorders (PADs) are monogenic diseases characterized by allergy or atopy‐related symptoms as fundamental features. In patients with PADs, primary immune deficiency and immune dysregulation symptoms are usually coexist. Chronic skin disease, manifesting with erythroderma, severe atopic dermatitis or eczema, and urticaria, is one of the main features observed in PADs, such as hyper‐IgE syndromes, Omenn syndrome, Wiskott‐Aldrich syndrome, IPEX‐linked syndrome, skin barrier disorders, as well as some autoinflammatory diseases. The recognition of PADs in the context of an allergic phenotype is crucial to ensure prompt diagnosis and appropriate treatment. This article provides an overview of the main PADs with skin involvement.

Quality improvement project to increase screening and referral for biologic therapy for patients with uncontrolled asthma

Background Asthma is a treatable chronic disease of airway inflammation with varying levels of control and severity. Biological therapy is an effective evidence-based treatment for patients with allergic and eosinophilic phenotypes of asthma who are classified as poorly controlled moderate to severe asthma. Yet, evidence-based treatments are infrequently used to support effective care of poorly controlled moderate and severe asthma. This quality improvement (QI) project aimed to increase the number of patients with uncontrolled moderate to severe asthma at an outpatient asthma center who are screened and referred for biologic therapy when appropriate. Methods A guideline-based biologic screening protocol was implemented using plan-do-study-act (PDSA) methodology allowing for a systematic approach for implementation, monitoring and making adjustments. A pre- and post-independent groups comparative design was utilized to evaluate screening and referral data. Results Screening improved significantly from pre- (n = 30, 23.8%) to post-implementation (n = 17, 70.8%), p < 0.001; phi = .372. Referrals to biologics also improved from 42.4% (n = 28) to 93.3% (n = 14), p < 0.001; phi = .396. Providers reported increased knowledge, confidence, and satisfaction with the asthma screening protocol at post-implementation. Conclusions The implementation of an asthma screening protocol for asthma patients in an ambulatory center is an effective way of increasing screening for eligibility for biologic therapy. Adhering to the standard of care based on evidence-based guidelines increased access to biologic therapy with a higher percentage of patients being referred for therapy.

Prospects in non-invasive diagnosis of bronchial asthma-related gastroesophageal reflux disease: a single-stage open uncontrolled non-randomised observational study

Background . Respiratory symptoms of bronchial asthma (BA) comorbid with gastroesophageal reflux disease (GERD) may provoke duodenogastroesophageal reflux (DGER) via aggressive agents like pepsinogens and bilirubin. Objectives . A clinical and functional study of the saliva pepsinogen and bilirubin-associated BA-comorbid GERD for non-invasive DGER diagnosis. Methods. A total of 29 patients with an allergic BA phenotype, comorbid GERD and 50 , 2 ± 2 , 4 years mean age have been examined. Biochemical blood panel included bilirubin, C-reactive protein and allergen-specifi c IgE. Saliva bilirubin was estimated in colorimetry, and the pepsinogen-1, -2 content — in immunological tests. Grade A–D reflux oesophagitis (RO) in oesophagoscopy was assigned to erosive reflux disease, and grade N–M oesophageal mucosa (OM) lesions — to non-erosive reflux disease. External respiratory function (ERF) was assessed with forced expiratory volume (FEV 1 , L/s), forced vital capacity (FVC), Tiffeneau index (FEV 1 /FVC), pre- and post-berodual FEF 1 and FVC dynamics. Results. The BA–GERD patients were markedly polymorbid. Cough and chest tightness associated with age, and the tight chest rate — with a higher body mass index and lower FEV 1 /FVC. The association between higher pepsinogen-I and lower FEV 1 /FVC–FVC in response to inhaled berodual, as well as between higher saliva bilirubin and lower FVC–FEV 1 after berodual intake reflects a significant high-DGER effect on BA representation. Conclusion. In BA–GERD patients, saliva pepsinogen and bilirubin are biomarkers of both DGER and respiratory inflammation with bronchospasm.

Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy.

Background. The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. Patients and methods. Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. Results. In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV1) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). Conclusion. The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

The Interplay Between Eczema and Breastfeeding Practices May Hide Breastfeeding’s Protective Effect on Childhood Asthma

Early allergic disease manifestations in infants may influence breastfeeding practices. In the current study, researchers sought to examine the relationship between breastfeeding duration and the development of asthma and allergic asthma phenotypes, stratified by a diagnosis of eczema during or after breastfeeding.Children who participated in the 6 year follow-up of the HealthNuts study, a population-based, longitudinal cohort study of allergic diseases in Australia.Children were enrolled between the ages of 11 and 15 months, and data regarding breastfeeding history, eczema diagnosis, environmental exposures, and family history of allergic disease were collected via questionnaire. At 6 years, information on wheeze, medication use, and parental report of physician-diagnosed asthma were obtained. Skin-prick testing to foods and aeroallergens at the age of 6 helped to stratify children with asthma into allergic and nonallergic phenotypes. From an original cohort of 5276 children, 3663 had completed questionnaires at 6 years, 3111 underwent skin testing, and 3632 had asthma data available for analysis. Children were characterized as never or ever breastfed. Of those breastfed, exclusive breastfeeding was categorized as never, <6 months, or >6 months. The overall duration of breastfeeding was treated as both a continuous (number of months) and categorical variable (<3 months, 3 to <6 months, 6 to <12 months, or >12 months).Children who did not participate in the full questionnaire at the age of 6 were more likely to be never breastfed, from a lower socioeconomic background, have one or both parents born outside of Australia, have no family history of allergic disease, and have had exposure to prenatal maternal or environmental smoking. Among children with asthma data, 96% were breastfed. At the age of 6, the prevalence of current asthma was 13%. Children with asthma were more likely to be male, have a parental history of asthma, have a family history of allergic disease, have been born preterm, have been born via cesarean delivery, and have been exposed to maternal smoking during pregnancy. Breastfeeding initiation was not associated with current asthma at the age of 6 years (adjusted odds ratio: 0.76) when compared with never breastfeeding. An increased duration of breastfeeding in children without eczema in infancy was associated with a reduced odds of asthma (per month increase; adjusted odds ratio: 0.98), which equates to a 0.86 reduced odds of asthma for a 6 month increase in breastfeeding. This association was not apparent in children who were diagnosed with eczema during breastfeeding.A longer duration of breastfeeding was associated with a reduced odds of asthma at the age pf 6 years among children without history of eczema in the first year. This association was masked before stratification of patients by history of eczema in infancy.Breastfeeding is known to be beneficial for improving many health outcomes. However, previous studies have not clearly demonstrated protective effects for breastfeeding on asthma. In the current study, a modest protective association was observed between an increased duration of breastfeeding and asthma but only among children who were not diagnosed with eczema in their first year. This association is complex because infantile eczema is a known risk factor for asthma and has also been shown to influence breastfeeding choices. Additional study is needed on the interplay between breastfeeding practices, early allergic manifestations, and the risk of subsequent allergic outcomes.

IgE-Based Therapeutic Combination Enhances Antitumor Response in Preclinical Models of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) represents 3% of all cancer cases and 7% of all cancer deaths in the United States. Late diagnosis and inadequate response to standard chemotherapies contribute to an unfavorable prognosis and an overall 5-year survival rate of less than 10% in PDAC. Despite recent advances in tumor immunology, tumor-induced immunosuppression attenuates the immunotherapy response in PDAC. To date, studies have focused on IgG-based therapeutic strategies in PDAC. With the recent interest in IgE-based therapies in multiple solid tumors, we explored the MUC1-targeted IgE potential against pancreatic cancer. Our study demonstrates the notable expression of FceRI (receptor for IgE antibody) in tumors from PDAC patients. Our study showed that administration of MUC1 targeted-IgE (mouse/human chimeric anti-MUC1.IgE) antibody at intermittent levels in combination with checkpoint inhibitor (anti-PD-L1) and TLR3 agonist (PolyICLC) induces a robust antitumor response that is dependent on NK and CD8 T cells in pancreatic tumor-bearing mice. Subsequently, our study showed that the antigen specificity of the IgE antibody plays a vital role in executing the antitumor response as nonspecific IgE, induced by ovalbumin (OVA), failed to restrict tumor growth in pancreatic tumor-bearing mice. Utilizing the OVA-induced allergic asthma-PDAC model, we demonstrate that allergic phenotype induced by OVA cannot restrain pancreatic tumor growth in orthotopic tumor-bearing mice. Together, our data demonstrate the novel tumor protective benefits of tumor antigen-specific IgE-based therapeutics in a preclinical model of pancreatic cancer, which can open new avenues for future clinical interventions.

Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans

Despite asthma has a considerable genetic component, an important proportion of genetic risks remain unknown, especially for non-European populations. Canary Islanders have the largest African genetic ancestry observed among Southwestern Europeans and the highest asthma prevalence in Spain. Here we examined broad chromosomal regions previously associated with an excess of African genetic ancestry in Canary Islanders, with the aim of identifying novel risk variants associated with asthma susceptibility. In a two-stage cases-control study, we revealed a variant within HLA-DQB1 significantly associated with asthma risk (rs1049213, meta-analysis p = 1.30 × 10–7, OR [95% CI] = 1.74 [1.41–2.13]) previously associated with asthma and broad allergic phenotype. Subsequent fine-mapping analyses of classical HLA alleles revealed a novel allele significantly associated with asthma protection (HLA-DQA1*01:02, meta-analysis p = 3.98 × 10–4, OR [95% CI] = 0.64 [0.50–0.82]) that had been linked to infectious and autoimmune diseases, and peanut allergy. HLA haplotype analyses revealed a novel haplotype DQA1*01:02-DQB1*06:04 conferring asthma protection (meta-analysis p = 4.71 × 10–4, OR [95% CI] = 0.47 [0.29– 0.73]).

First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy

To examine the effectiveness and safety of peanut oral immunotherapy (POIT) after 1 year of maintenance in preschool-aged children.In the study, researchers included 161 patients aged 9 to 70 months who successfully completed 1 year of maintenance POIT and were eligible for follow-up oral food challenge (OFC). The inclusion criteria were having a history of objective reaction to peanut and a positive test result (either a skin-prick test [SPT] or peanut-specific immunoglobulin E [ps-IgE]) or at least 1 objective reaction with dosing during build-up, along with a predetermined ps-IgE level and SPT wheal size.Preschoolers enrolled in the study were given gradually increasing peanut protein doses over 16–22 weeks at clinic visits, building up to a maintenance dose of 300 mg. The children then ingested 300 mg of peanut protein daily for a year. After ∼12 months, the participants were invited to participate in a follow-up peanut OFC. SPT and/or ps-IgE were obtained at baseline and selectively throughout the maintenance and follow-up OFC visits. Symptoms of allergic reactions occurring were recorded and graded 1 to 5.Of the patients who received a year of maintenance therapy and underwent follow-up OFC (n = 117), 92 (78.6%) tolerated a cumulative dose of 4000 mg peanut protein without any symptoms, and 115 (98.3%) tolerated at least 1000 mg. The dose tolerated had increased on average by 3969 mg in those with a negative follow-up OFC and by 3376 mg in those with a positive follow-up OFC. SPT wheal size was also significantly decreased after a year regardless of follow-up OFC result; however, the decrease in ps-IgE was not statistically significant. Those with reactions at the follow-up OFC had either grade 1 (14.5% of all who underwent OFC), grade 2 (6%), or grade 3 (0.85%). No one had a grade 4 or 5 reaction. Of the 124 patients with safety outcomes analyzed during maintenance therapy, 111 (89.5%) were symptom-free during POIT dosing, 10 (8.1%) had grade 1 reactions, 3 (2.4%) had grade 2 reactions, and only 2 (1.6%) required epinephrine for POIT dosing reactions.POIT is effective for preschoolers, protecting against at least 1000 mg peanut protein exposure after one year of maintenance therapy in 98.3% of children and allowing consumption of up to 4000 mg in 78.6%. It is also safe during maintenance, with nearly 90% of children symptom-free during maintenance dosing.POIT has emerged as a patient-preference–sensitive option to increase tolerance to peanut protein and protect against accidental exposure. Previous studies have revealed that increasing the peanut threshold to 1000 mg provides 99% protection from accidental exposures, and commercial POIT product is now approved in children 4 to 17 years old. This is the first real-world study revealing that the majority of preschoolers (98.3%) are able to tolerate 1000 mg after a year of POIT maintenance therapy. Mounting evidence suggests POIT may be safer and more effective when initiated at younger ages, likely because of a milder allergic phenotype, less patient aversion, and opportunity for better adherence from close parental supervision. Preschool POIT is a promising disease-modifying intervention that, in the context of shared decision-making with an experienced pediatric allergist, is likely to dramatically improve health and economic outcomes for patients and families.

Mapping Sequential IgE-Binding Epitopes on Major and Minor Egg Allergens

Introduction: Molecular studies of hen’s egg allergens help define allergic phenotypes, with IgE to sequential (linear) epitopes on the ovomucoid (OVM) protein associated with a persistent disease. Epitope profiles of other egg allergens are largely unknown. The objective of this study was to construct an epitope library spanning across 7 allergens and further evaluate sequential epitope-specific (ses-)IgE and ses-IgG₄ among baked-egg reactive or tolerant children. Methods: A Bead-Based Epitope Assay was used to identify informative IgE epitopes from 15-mer overlapping peptides covering the entire OVM and ovalbumin (OVA) proteins in 38 egg allergic children. An amalgamation of 12 B-cell epitope prediction tools was developed using experimentally identified epitopes. This ensemble was used to predict epitopes from ovotransferrin, lysozyme, serum albumin, vitellogenin-II fragment, and vitellogenin-1 precursor. Ses-IgE and ses-IgG₄ repertoires of 135 egg allergic children (82 reactive to baked-egg, the remaining 52 tolerant), 46 atopic controls, and 11 healthy subjects were compared. Results: 183 peptides from OVM and OVA were screened and used to create an aggregate algorithm, improving predictions of 12 individual tools. A final library of 65 sequential epitopes from 7 proteins was constructed. Egg allergic children had higher ses-IgE and lower ses-IgG₄ to predominantly OVM epitopes than both atopic and healthy controls. Baked-egg reactive children had similar ses-IgG₄ but greater ses-IgE than tolerant group. A combination of OVA-sIgE with ses-IgEs to OVM-023 and OVA-028 was the best predictor of reactive phenotype. Conclusion: We have created a comprehensive epitope library and showed that ses-IgE is a potential biomarker of baked-egg reactivity.

Characterization of T2-Low and T2-High Asthma Phenotypes in Real-Life.

Asthma is a heterogeneous and complex condition characterized by chronic airway inflammation, which may be clinically stratified into three main phenotypes: type 2 (T2) low, T2-high allergic, and T2-high non-allergic asthma. This real-world study investigated whether phenotyping patients with asthma using non-invasive parameters could be feasible to characterize the T2-low and T2-high asthma phenotypes in clinical practice. This cross-sectional observational study involved asthmatic outpatients (n = 503) referring to the Severe Asthma Centre of the San Luigi Gonzaga University Hospital. Participants were stratified according to the patterns of T2 inflammation and atopic sensitization. Among outpatients, 98 (19.5%) patients had T2-low asthma, 127 (25.2%) T2-high non-allergic, and 278 (55.3%) had T2-high allergic phenotype. In comparison to T2-low, allergic patients were younger (OR 0.945, p < 0.001) and thinner (OR 0.913, p < 0.001), had lower smoke exposure (OR 0.975, p < 0.001) and RV/TLC% (OR 0.950, p < 0.001), higher prevalence of asthma severity grade 5 (OR 2.236, p < 0.05), more frequent rhinitis (OR 3.491, p < 0.001) and chronic rhinosinusitis with (OR 2.650, p < 0.001) or without (OR 1.919, p < 0.05) nasal polyps, but less common arterial hypertension (OR 0.331, p < 0.001). T2-high non-allergic patients had intermediate characteristics. Non-invasive phenotyping of asthmatic patients is possible in clinical practice. Identifying characteristics in the three main asthma phenotypes could pave the way for further investigations on useful biomarkers for precision medicine.

P066 DUPILUMAB EFFICACY IN PATIENTS WITH TYPE 2 ASTHMA WITH/WITHOUT ALLERGIC PHENOTYPE RECEIVING HIGH-DOSE INHALED CORTICOSTEROIDS

Dupilumab blocks the shared receptor component for IL-4/IL-13, key and central drivers of type 2 (T2) inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), add-on dupilumab 200/300mg every 2 weeks, vs placebo, significantly reduced severe exacerbations, improved pre-bronchodilator FEV1, and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma. Treatment effects were greater in patients with elevated baseline T2 biomarkers (blood eosinophils ≥150cells/μL or FeNO ≥25ppb). This post hoc analysis assessed dupilumab efficacy in patients with T2 asthma on high-dose inhaled corticosteroids (ICS) with/without an allergic phenotype.

LncRNA MIAT Promotes Allergic Inflammation and Symptoms by Targeting MiR-10b-5p in Allergic Rhinitis Mice.

Allergic rhinitis (AR) is one of the most common noninfectious respiratory diseases caused by immunoglobulin E (IgE) response. The study sought to explore the relationship between lncRNA MIAT and miR-10b-5p and their interaction in the regulation of allergic phenotypes in allergic rhinitis (AR) mice. A mice model of AR was constructed using ovalbumin (OVA) sensitization. AR mice were treated with miR-10b-5p agomiR and LNA mediated lncRNA MIAT. The targeting relationship between MIAT and miR-10b-5p was analyzed by the ENCORI website and dual-luciferase reporter assay. The numbers of rubbing and sneezing of mice were counted. Hematoxylin-eosin (HE) staining visualized the eosinophils infiltration in nasal mucosa tissues of mice. The percentage of Th17 cells was quantitated by flow cytometry analysis. ELISA was used to detect the levels of serum OVA-specific IgE, the Th12 cytokine IL-4, and inflammatory cytokines (IL-6, IL-17). MIAT was up-regulated in the nasal mucosa of AR mice, while miR-10b-5p was down-regulated. MIAT directly suppressed miR-10b-5p expression in AR mice. The numbers of rubbing and sneezing, the percentage of Th17 cells, and the levels of OVA-specific IgE, IL-4, IL-6, and IL-17 in AR mice were decreased by miR-10b-5p overexpression, which was reversed by MIAT overexpression. The eosinophils infiltration in AR mice was inhibited by miR-10b-5p overexpression, which was also reversed by MIAT overexpression. The present study demonstrates that MIAT overexpression Promotes allergic inflammation and symptoms by activating Th17 immune response via miR-10b-5p inhibition.

Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide

BackgroundInhalation of fungal spores is a strong risk factor for severe asthma and experimentally leads to development of airway mycosis and asthma-like disease in mice. However, in addition to fungal spores, humans are simultaneously exposed to other inflammatory agents such as lipopolysaccharide (LPS), with uncertain relevance to disease expression. To determine how high dose inhalation of LPS influences the expression of allergic airway disease induced by the allergenic mold Aspergillus niger (A. niger).MethodsC57BL/6J mice were intranasally challenged with the viable spores of A. niger with and without 1 μg of LPS over two weeks. Changes in airway hyperreactivity, airway and lung inflammatory cell recruitment, antigen-specific immunoglobulins, and histopathology were determined.ResultsIn comparison to mice challenged only with A. niger, addition of LPS (1 μg) to A. niger abrogated airway hyperresponsiveness and strongly attenuated airway eosinophilia, PAS+ goblet cells and TH2 responses while enhancing TH1 and TH17 cell recruitment to lung. Addition of LPS resulted in more severe, diffuse lung inflammation with scattered, loosely-formed parenchymal granulomas, but failed to alter fungus-induced IgE and IgG antibodies.ConclusionsIn contrast to the strongly allergic lung phenotype induced by fungal spores alone, addition of a relatively high dose of LPS abrogates asthma-like features, replacing them with a phenotype more consistent with acute hypersensitivity pneumonitis (HP). These findings extend the already established link between airway mycosis and asthma to HP and describe a robust model for further dissecting the pathophysiology of HP.