Background: Mites are the most prevalent source of indoor allergens. The present study used a component-resolved diagnosis (CRD) approach to investigate the mite-specific IgE sensitization profile for Dermatophagoides pteronyssinus and Blomia tropicalis. We also assessed the performance of a commercially available CRD approach in patients with severe allergic rhinitis. Methods: We selected 63 consecutive patients with dual sensitization to D pteronyssinus and B tropicalis and persistent severe rhinitis according to the ARIA guidelines. We performed skin prick tests with standardized extracts and determined specific serum IgE to both mites, along with serum specific IgE to Der p 1, Der p 2, Der p 23, Der p 10, and Blo t 5. Results: Fifty-eight and 59 patients had positive sIgE to the whole extracts of D pteronyssinus and B tropicalis, respectively. While 91.67% of patients were sensitized to specific IgE to Der p 1, Der p 2, and/or Der p 23, specific IgE to Blo t 5 (≥0.3 ISU-E) was not detected in most of the serum samples (55%). Conclusions: Although the combination panel of the commercially available major allergens Der p 1, Der p 2, and Der p 23 identified more than 90% of the D pteronyssinus–allergic patients, Blo t 5 performed somewhat poorly in those sensitized to B tropicalis. Improvements in CRD and further research concerning the prevalence and clinical relevance of serodominant allergens are needed to achieve a genuine molecular diagnosis, as well as patient-centered mite allergy–specific immunotherapy.

Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi‐ancestry meta‐analysis of genome‐wide association studies (meta‐GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression.Methods: A meta‐GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10⁻⁵) were assessed for replication in 36,477 European and 1078 non‐European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico.Results: One hundred and twenty‐six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule‐1/exostosin like glycosyltransferase‐2 (VCAM1/EXTL2) (discovery: odds ratio (OR_{T allele}) = 0.82, p = 9.05 × 10⁻⁶ and replication: OR_{T allele} = 0.89, p = 5.35 × 10⁻³) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR_{C allele} = 0.85, p = 3.10 × 10⁻⁵ and replication: OR_{C allele} = 0.89, p = 1.30 × 10⁻²). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood.Conclusions: This multi‐ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.

Climate change and exposure to environmental pollutants play a key role in the onset and aggravation of allergic diseases. As different climate-dependent patterns of molecular immunoglobulin E (IgE) reactivity have been regionally described, we sought to investigate the evolving allergen exposome in distinctive allergic phenotypes and subtropical weather conditions through a Precision Allergy Molecular Diagnosis (PAMD@) model. Concurrent sensitization to several house dust mites (HDM) and storage mite molecules were broadly dominant in the investigated cohort, followed by the major cat allergen Fel d 1, and regardless of the basal allergic disease. Although a complex repertoire of allergens was recognized, a steadily increasing number of IgE binding molecules was associated with the complexity of the underlying atopic disease. Besides the highly prevalent IgE responses to major HDM allergens, Der p 21, Der p 5, and Der p 7 also showed up as serodominant molecules, especially in subjects bothered by asthma and atopic dermatitis. The accurate characterization of the external exposome at the molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease in terms of personalized diagnosis and therapy.

Omalizumab, a humanized monoclonal anti-IgE antibody has the potential to alter allergen processing. Recently, it has been postulated the assessment of PHA-stimulated adenosine triphosphate (ATP) activity as maker of CD4+ T cells activity in peripheral blood cells. We present the case report of a 35-year-old woman with a history of chronic idiopathic urticaria and angioedema of 8 years of development with poor response to treatment. The patient was partially controlled with cyclosporine at doses of 100 mg/12 h. However, she was still developing hives daily. Finally treatment with omalizumab was started at dose of 300 mg every 2 weeks. The patient experienced a decrease in urticarial lesions 2 days after starting therapy. We also evaluated the effects of omalizumab therapy on the activity of peripheral blood CD4+ T cells from the patient, in order to determine the potential modification of anti-IgE therapy on the process of antigen presentation-recognition. Activity of CD4+ cells by ATP release was clearly increased demonstrating an enlarged CD4 activity. Omalizumab may be useful in the treatment of severe chronic urticaria. ATP activity of peripheral blood CD4+ T cells might be a non-subjective method to assess Omalizumab activity.

Asthma exacerbations are a major contributor to the global disease burden, but no significant predictive biomarkers are known. The Genomics and Metagenomics of Asthma Severity (GEMAS) study aims to assess the role of genomics and the microbiome in severe asthma exacerbations. Here, we present the design of GEMAS and the characteristics of patients recruited from March 2018 to March 2020. Different biological samples and demographic and clinical variables were collected from asthma patients recruited by allergy and pulmonary medicine units in several hospitals from Spain. Cases and controls were defined by the presence/absence of severe asthma exacerbations in the past year (oral corticosteroid use, emergency room visits, and/or asthma-related hospitalizations). A total of 137 cases and 120 controls were recruited. After stratifying by recruitment location (i.e., Canary Islands and Basque Country), cases and controls did not differ for most demographic and clinical variables (p > 0.05). However, cases showed a higher proportion of characteristics inherent to asthma exacerbations (impaired lung function, severe disease, uncontrolled asthma, gastroesophageal reflux, and use of asthma medications) compared to controls (p < 0.05). Similar results were found after stratification by recruitment unit. Thereby, asthma patients enrolled in GEMAS are balanced for potential confounders and have clinical characteristics that support the phenotype definition. GEMAS will improve the knowledge of potential biomarkers of asthma exacerbations.

Skin prick testing is the first-line interventional method to diagnose IgE mediated allergic diseases. Methodological differences in manufacturing processes and extract standardization may lead to variations in the reagent quality and potency. The current study evaluates sixteen commercially available Dermatophagoides pteronyssinus and Blomia tropicalis extracts for allergy diagnosis from different European manufacturers regarding allergen composition and content and whether these differences could influence their biological activity. Mite-allergic subjects (n = 21) were skin-tested with the extracts and studied for immunoglobulin E reactivity. Nine extracts from D. pteronyssinus and seven from B. tropicalis were analysed for total protein content by Bradford and ELISA double sandwich was used to quantify specific antibodies for D. pteronyssinus and B. tropicalis major allergens from nine different manufacturers. Mite extracts showed a 10–60 fold variation regarding the total protein content. The contents of the major allergens of D. pteronyssinus and B. tropicalis differed considerably (30–53 fold change) among the extracts. Blo t 5 was quantitatively present in < 50% of the of the B. tropicalis reagents and could not be clearly detected by immunoblotting in the majority of the B. tropicalis commercial extracts. Certain natural D. pteronyssinus and B. tropicalis extracts lack important allergens showing a considerable variability in composition and content. A closer collaboration among clinicians, allergen manufacturing companies and regulatory agencies to improve the quality and consistency of D. pteronyssinus and B. tropicalis extracts is warranted to achieve a more precise diagnosis and treatment of house dust mite allergy.